Miracle-dz/UniFAR-FTUs huggingface dataset:
The Unprecedented Growth in Medical Admissions in the UK: The Ageing Population or a Possible Infectious/Immune Aetiology?

Past and recent trends in medical and other admissions in England are examined to determine if the increasing elderly population is the sole source for pressures in the NHS arising from large increases in medical admissions. Unusual step-like events appear to lie behind the unexplained growth in medical admissions. Age banded trends since 2012/13 show evidence for age-specific patterns of growth which are similar to patterns in immunity arising from antigenic original sin, i.e. repeated priming of the immune system and consequent antibody landscapes arising from lifetime exposure to different strains of the same agent. Contrary to common belief, age-standardised growth in medical group (general and elderly medicine, etc.) admissions is highest in the younger age bands, except for children. As opposed to the medical group, age standardised growth in the oncology (oncology, radiotherapy) group occurs to the greatest extent in the youngest and oldest. Periods of unexplained higher deaths which accompany these events have been overlooked by traditional disease surveillance methods, and hidden patterns in deaths can be revealed by the use of cumulative sum of deviations from the mean (CUSUM), and running 12 month total analysis. Interactions between a suspected infectious agent and influenza appear likely. Changes in the gender ratio at birth around the time of the 1918 ‘Spanish flu’ epidemic suggest the potential involvement of a second agent. The pattern of conditions most affected shows some evidence for common immune function aetiology, and the immune modifying virus cytomegalovirus may be in some way involved in these events either as cause or via opportunistic reactivation.
NDVI as indicator of degradation

Unasylva 238, Vol. 62, 2011/2 Carmen Lourdes Meneses-Tovar is Submanager for Remote Sensing, National Forestry Commission of Mexico. Forest degradation has become a serious problem, especially in developing countries. In 2000, the total area of degraded forest in 77 countr ies was estimated at 800 million hectares (ha), 500 million ha of which had changed from primary to secondary vegetation (ITTO, 2002). Among other impacts, the process of forest degradation represents a significant proportion of greenhouse gas emissions. There is an urgent need to measure and analyse it, in order to design action to reverse the process. This article describes how one method of analysing remote sensing data in conjunction with field data to monitor forest degradation was put into practice. It presents a study carried out to identify relationships between indicators of forest functions and the normalized difference vegetation index (NDVI), which is estimated through analysis of satellite images to give an indication of “greenness”. The premise is that NDVI is an indicator of vegetation health, because degradation of ecosystem vegetation, or a decrease in green, would be reflected in a decrease in NDVI value. Therefore, if a relationship between the quantity of an indicator – aerial biomass – in various forest ecosystems and the NDVI can be identified, processes of degradation can be monitored. NDVI as indicator of degradation
Effectiveness of Paper , VR and Stereo-VR in the Delivery of Instructions for Assembly Tasks

A study was conducted to compare the relative performance, in terms of completion time and accuracy, of desktop virtual reality, desktop stereo virtual reality, and a paper-based approach in presenting assembly instructions for 3D construction tasks. All presentations depicted a single step of the assembly process at a time. The results showed no significant differences in accuracy between any of the three approaches. In terms of interaction, a comparison of the two computer based presentations revealed that users rotated the model less frequently in the 3D stereo graphics than in the standard graphics, suggesting that more information was communicated by the stereo approach. The results also reveal that object complexity significantly impacts user performance with regards to time and that presentations of real-world assembly tasks will benefit from enhanced attention to inter-spatial relationships.
Lower-Dimensional Video Discriminators for Generative Adversarial Networks

aRobust Autonomy and Decisions Group, The School of Informatics, The University of Edinburgh, 10 Crichton St, Edinburgh EH8 9AB bThe Edinburgh Centre of Robotics, The University of Edinburgh’s Bayes Centre, 47 Potterrow, Edinburgh EH8 9BT cThe School of Engineering and Physical Sciences, The Robotarium, Heriot-Watt University, Edinburgh, EH14 4AS dFiveAI, 5th Floor, Greenside, 12 Blenheim Place, Edinburgh, EH7 5JH
Intensity Modulated Radiotherapy (IMRT) With Carbon Ion Boost in the Multimodal Treatment of Salivary Duct Carcinoma

Background: To assess outcomes and treatment related toxicity following intensity-modulated radiotherapy (IMRT) and a Carbon Ion Radiotherapy (CIRT) boost for salivary duct carcinoma (SDC). Methods: Twenty-eight consecutive patients with SDC who underwent a postoperative (82%) or definitive (18%) radiation therapy between 2010 and 2017 were assessed in this retrospective single-center analysis. CIRT boost was delivered with median 18 Gy(RBE) in 6 daily fractions, followed by an TomoTherapy®-based IMRT (median 54 Gy in 27 daily fractions). Treatment-related acute toxicity was assessed according to CTCAE Version 4. Results: Tumors were most commonly located in the major salivary glands (n = 25; 89%); 23 patients (82%) received previous surgery (R0: 30%; R1: 57%; R2: 4%; RX: 19%). Median follow-up was 30 months. Four patients (14%) experienced a local relapse and 3 (11%) developed locoregional recurrence. The two-year local control (LC) and locoregional control (LRC) was 96 and 93%, respectively. Median disease-free survival (DFS) was 27 months, metastasis-free survival (MFS) was 69 months, and overall survival (OS) was 93 months. Acute grade 3 toxicity occurred in 11 patients (mucositis, dermatitis, xerostomia; n = 2 each (7%) were the most common) and 2 osteonecroses of the mandibular (grade 3) occurred. No patients experienced grade ≥4 toxicities. Conclusions: Multimodal therapy approaches with surgery followed by IMRT and CIRT boost for SDC leads to good local and locoregional disease control. However, the frequent occurrence of distant metastases limits the prognosis and requires optimization of adjuvant systemic therapies.
Unraveling the Molecular Signature of Extracellular Vesicles From Endometrial-Derived Mesenchymal Stem Cells: Potential Modulatory Effects and Therapeutic Applications

Endometrial-derived Mesenchymal Stem Cells (endMSCs) are involved in the regeneration and remodeling of human endometrium, being considered one of the most promising candidates for stem cell-based therapies. Their therapeutic effects have been found to be mediated by extracellular vesicles (EV-endMSCs) with pro-angiogenic, anti-apoptotic, and immunomodulatory effects. Based on that, the main goal of this study was to characterize the proteome and microRNAome of these EV-endMSCs by proteomics and transcriptomics approaches. Additionally, we hypothesized that inflammatory priming of endMSCs may contribute to modify the therapeutic potential of these vesicles. High-throughput proteomics revealed that 617 proteins were functionally annotated as Extracellular exosome (GO:0070062), corresponding to the 70% of the EV-endMSC proteome. Bioinformatics analyses allowed us to identify that these proteins were involved in adaptive/innate immune response, complement activation, antigen processing/presentation, negative regulation of apoptosis, and different signaling pathways, among others. Of note, multiplexed quantitative proteomics and Systems Biology analyses showed that IFNγ priming significantly modulated the protein profile of these vesicles. As expected, proteins involved in antigen processing and presentation were significantly increased. Interestingly, immunomodulatory proteins, such as CSF1, ERAP1, or PYCARD were modified. Regarding miRNAs expression profile in EV-endMSCs, Next-Generation Sequencing (NGS) showed that the preferred site of microRNAome targeting was the nucleus (n = 371 microTargets), significantly affecting signal transduction (GO:0007165), cell proliferation (GO:0008283), and apoptotic processes (GO:0006915), among others. Interestingly, NGS analyses highlighted that several miRNAs, such as hsa-miR-150-5p or hsa-miR-196b-5p, were differentially expressed in IFNγ-primed EV-endMSCs. These miRNAs have a functional involvement in glucocorticoid receptor signaling, IL-6/8/12 signaling, and in the role of macrophages. In summary, these results allowed us to understand the complexity of the molecular networks in EV-endMSCs and their potential effects on target cells. To our knowledge, this is the first comprehensive study based on proteomic and genomic approaches to unravel the therapeutic potential of these extracellular vesicles, that may be used as immunomodulatory effectors in the treatment of inflammatory conditions.
Comparative Genomics of Streptococcus thermophilus Support Important Traits Concerning the Evolution, Biology and Technological Properties of the Species

Streptococcus thermophilus is a major starter for the dairy industry with great economic importance. In this study we analyzed 23 fully sequenced genomes of S. thermophilus to highlight novel aspects of the evolution, biology and technological properties of this species. Pan/core genome analysis revealed that the species has an important number of conserved genes and that the pan genome is probably going to be closed soon. According to whole genome phylogeny and average nucleotide identity (ANI) analysis, most S. thermophilus strains were grouped in two major clusters (i.e., clusters A and B). More specifically, cluster A includes strains with chromosomes above 1.83 Mbp, while cluster B includes chromosomes below this threshold. This observation suggests that strains belonging to the two clusters may be differentiated by gene gain or gene loss events. Furthermore, certain strains of cluster A could be further subdivided in subgroups, i.e., subgroup I (ASCC 1275, DGCC 7710, KLDS SM, MN-BM-A02, and ND07), II (MN-BM-A01 and MN-ZLW-002), III (LMD-9 and SMQ-301), and IV (APC151 and ND03). In cluster B certain strains formed one distinct subgroup, i.e., subgroup I (CNRZ1066, CS8, EPS, and S9). Clusters and subgroups observed for S. thermophilus indicate the existence of lineages within the species, an observation which was further supported to a variable degree by the distribution and/or the architecture of several genomic traits. These would include exopolysaccharide (EPS) gene clusters, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-CRISPR associated (Cas) systems, as well as restriction-modification (R-M) systems and genomic islands (GIs). Of note, the histidine biosynthetic cluster was found present in all cluster A strains (plus strain NCTC12958T) but was absent from all strains in cluster B. Other loci related to lactose/galactose catabolism and urea metabolism, aminopeptidases, the majority of amino acid and peptide transporters, as well as amino acid biosynthetic pathways were found to be conserved in all strains suggesting their central role for the species. Our study highlights the necessity of sequencing and analyzing more S. thermophilus complete genomes to further elucidate important aspects of strain diversity within this starter culture that may be related to its application in the dairy industry.
Current and Future Treatment Strategies for Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, and can be subcategorized histologically and/or based on PAX-FOXO1 fusion gene status. Over the last four decades, there have been no significant improvements in clinical outcomes for advanced and metastatic RMS patients, underscoring a need for new treatment options for these groups. Despite significant advancements in our understanding of the genomic landscape and underlying biological mechanisms governing RMS that have informed the identification of novel therapeutic targets, development of these therapies in clinical trials has lagged far behind. In this review, we summarize the current frontline multi-modality therapy for RMS according to pediatric protocols, highlight emerging targeted therapies and immunotherapies identified by preclinical studies, and discuss early clinical trial data and the implications they hold for future clinical development.
Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.
Paracrine Fibroblast Growth Factor 1 Functions as Potent Therapeutic Agent for Intrahepatic Cholestasis by Downregulating Synthesis of Bile Acid

Endocrine fibroblast growth factor (FGF) 19 has been shown to be capable of maintaining bile acid (BA) homeostasis and thus hold promise to be a potential therapeutic agent for cholestasis liver disease. However, whether paracrine FGFs possess this BA regulatory activity remains to be determined. In our study, we identified that paracrine fibroblast growth factor 1 (FGF1) was selectively downregulated in the liver of alpha naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis mice, suggesting a pathological relevance of this paracrine FGF with abnormal BA metabolism. Therefore, we evaluated the effects of engineered FGF1 mutant - FGF1ΔHBS on the metabolism of hepatic BA and found that this protein showed a more potent inhibitory effect of BA biosynthesis than FGF19 without any hepatic mitogenic activity. Moreover, the chronic administration of FGF1ΔHBS protected liver against ANIT-induced injury by reducing hepatic BA accumulation. Taken together, these data suggest that FGF1ΔHBS may function as a potent therapeutic agent for intrahepatic cholestasis liver disease.
Association Between Hearing and Vision Impairment and Risk of Dementia: Results of a Case-Control Study Based on Secondary Data

Introduction: Hearing and vision loss are highly prevalent in elderly adults, and thus frequently occur in conjunction with cognitive impairments. Studies have shown that hearing impairment is associated with a higher risk of dementia. However, evidence concerning the association between vision loss and dementia, as well as the co-occurrence of vision and hearing loss and dementia, has been inconclusive. Objectives: To assess the association between: (i) either hearing or vision loss and the risk of dementia, as well as between; and (ii) the combination of both sensory impairments and the risk of dementia. Methods: This case-control study was based on a 5-year data set that included patients aged 65 years and older who had initially been diagnosed with dementia diseases by one of 1,203 general practitioners in Germany between January 2013 and December 2017. In total, 61,354 identified dementia cases were matched to non-dementia controls, resulting in a sample size of 122,708 individuals. Hearing loss and vision loss were identified using the ICD-10 diagnoses documented in the general practitioners’ files prior to the initial dementia diagnosis. Multivariate logistic regression models were fitted to evaluate the associations between visual and/or hearing impairment and the risk of dementia and controlled for sociodemographic and clinical variables. Results: Hearing impairment was documented in 11.2% of patients with a dementia diagnosis and 9.5% of patients without such a diagnosis. Some form of vision impairment was documented in 28.4% of patients diagnosed with dementia and 28.8% of controls. Visual impairment was not significantly associated with dementia (OR = 0.97, CI = 95% 0.97–1.02, p = 0.219). However, patients with hearing impairment were at a significantly higher risk of developing dementia (OR = 1.26, CI = 95% 1.15–1.38, p < 0.001), a finding that very likely led to the observed significant association of the combination of both visual and hearing impairments and the risk of dementia (OR = 1.14, CI = 95% 1.04–1.24, p = 0.005). Discussion: This analysis adds important evidence that contributes to the limited body of knowledge about the association between hearing and/or vision loss and dementia. It further demonstrates that, of the two, only hearing impairment affects patients’ cognition and thus contributes to dementia risk.
Similar Expectation Effects for Immediate and Delayed Stimulus Repetitions

A prior cue or stimulus allows prediction of the future occurrence of an event and therefore reduces the associated neural activity in several cortical areas. This phenomenon is labeled expectation suppression (ES) and has recently been shown to be independent of the generally observed effects of stimulus repetitions (repetition suppression, RS: reduced neuronal response after the repetition of a given stimulus). While it has been shown that attentional cueing is strongly affected by the length of the cue-target delay, we have no information on the temporal dynamics of expectation effects, as in most prior studies of ES the delay between the predictive cue and the target (i.e., the inter-stimulus interval, ISI) was in the range of a few hundred milliseconds. Hence, we presented participants with pairs of faces where the first face could be used to build expectations regarding the second one, in the sense that one gender indicated repetition of the same face while the other gender predicted the occurrence of novel faces. In addition, we presented the stimulus pairs with two different ISIs (0.5 s for Immediate and 1.75 or 3.75 s for Delayed ISIs). We found significant RS as well as a reduced response for correctly predicted when compared to surprising trials in the fusiform face area. Importantly, the effects of repetition and expectation were both independent of the length of the ISI period. This implies that Immediate and Delayed cue-target stimulus arrangements lead to similar expectation effects in the face sensitive-visual cortex.
Intense Physical Exercise Induces an Anti-inflammatory Change in IgG N-Glycosylation Profile

Exercise is known to improve many aspects of human health, including modulation of the immune system and inflammatory status. It is generally understood that exercise reduces inflammation, but there are missing links in terms of understanding the mechanisms as well as the differences between exercise modalities. N-glycosylation of immunoglobulin G (IgG) and total plasma proteins was previously shown to reflect changes in inflammatory pathways, which could provide valuable information to further clarify exercise effects. In order to further expand the understanding of the relationship between physical activity and inflammation, we examined the effect of intense exercise, in the form of repeated sprint training (RST), on IgG and total plasma proteins N-glycosylation in combination with traditionally used inflammation markers: C-reactive protein (CRP), interleukin 6 (IL-6), and leukocyte count. Twenty-nine male physical education students were separated into treatment (RST, N = 15) and control (N = 14) groups. The RST group completed a 6-week exercise protocol while the control group was instructed to refrain from organized physical activity for the duration of the study. Three blood samples were taken at different time points: prior to start of the training program, the final week of the exercise intervention (EXC), and at the end of the 4-week recovery period (REC). Following the end of the recovery period IgG N-glycosylation profiles showed anti-inflammatory changes in RST group compared to the control group, which manifested as a decrease in agalactosylated (p = 0.0473) and an increase in digalactosylated (p = 0.0473), and monosialylated (p = 0.0339) N-glycans. Plasma protein N-glycans didn’t change significantly, while traditional inflammatory markers also didn’t show significant change in inflammatory status. Observed results demonstrate the potential of intense physical exercise to reduce levels of systemic basal inflammation as well as the potential for IgG N-glycosylation to serve as a sensitive longitudinal systemic inflammation marker.
Multi-Disease Segmentation of Gliomas and White Matter Hyperintensities in the BraTS Data Using a 3D Convolutional Neural Network

An important challenge in segmenting real-world biomedical imaging data is the presence of multiple disease processes within individual subjects. Most adults above age 60 exhibit a variable degree of small vessel ischemic disease, as well as chronic infarcts, which will manifest as white matter hyperintensities (WMH) on brain MRIs. Subjects diagnosed with gliomas will also typically exhibit some degree of abnormal T2 signal due to WMH, rather than just due to tumor. We sought to develop a fully automated algorithm to distinguish and quantify these distinct disease processes within individual subjects’ brain MRIs. To address this multi-disease problem, we trained a 3D U-Net to distinguish between abnormal signal arising from tumors vs. WMH in the 3D multi-parametric MRI (mpMRI, i.e., native T1-weighted, T1-post-contrast, T2, T2-FLAIR) scans of the International Brain Tumor Segmentation (BraTS) 2018 dataset (ntraining = 285, nvalidation = 66). Our trained neuroradiologist manually annotated WMH on the BraTS training subjects, finding that 69% of subjects had WMH. Our 3D U-Net model had a 4-channel 3D input patch (80 × 80 × 80) from mpMRI, four encoding and decoding layers, and an output of either four [background, active tumor (AT), necrotic core (NCR), peritumoral edematous/infiltrated tissue (ED)] or five classes (adding WMH as the fifth class). For both the four- and five-class output models, the median Dice for whole tumor (WT) extent (i.e., union of AT, ED, NCR) was 0.92 in both training and validation sets. Notably, the five-class model achieved significantly (p = 0.002) lower/better Hausdorff distances for WT extent in the training subjects. There was strong positive correlation between manually segmented and predicted volumes for WT (r = 0.96) and WMH (r = 0.89). Larger lesion volumes were positively correlated with higher/better Dice scores for WT (r = 0.33), WMH (r = 0.34), and across all lesions (r = 0.89) on a log(10) transformed scale. While the median Dice for WMH was 0.42 across training subjects with WMH, the median Dice was 0.62 for those with at least 5 cm3 of WMH. We anticipate the development of computational algorithms that are able to model multiple diseases within a single subject will be a critical step toward translating and integrating artificial intelligence systems into the heterogeneous real-world clinical workflow.