Miracle-dz/UniFAR-FTUs huggingface dataset:
Automatic detection of papilledema through fundus retinal images using deep learning

Papilledema is a syndrome of the retina in which retinal optic nerve is inflated by elevation of intracranial pressure. The papilledema abnormalities such as retinal nerve fiber layer (RNFL) opacification may lead to blindness. These abnormalities could be seen through capturing of retinal images by means of fundus camera. This paper presents a deep learning‐based automated system that detects and grades the papilledema through U‐Net and Dense‐Net architectures. The proposed approach has two main stages. First, optic disc and its surrounding area in fundus retinal image are localized and cropped for input to Dense‐Net which classifies the optic disc as papilledema or normal. Second, consists of preprocessing of Dense‐Net classified papilledema fundus image by Gabor filter. The preprocessed papilledema image is input to U‐Net to achieve the segmented vascular network from which the vessel discontinuity index (VDI) and vessel discontinuity index to disc proximity (VDIP) are calculated for grading of papilledema. The VDI and VDIP are standard parameter to check the severity and grading of papilledema. The proposed system is evaluated on 60 papilledema and 40 normal fundus images taken from STARE dataset. The experimental results for classification of papilledema through Dense‐Net are much better in terms of sensitivity 98.63%, specificity 97.83%, and accuracy 99.17%. Similarly, the grading results for mild and severe papilledema classification through U‐Net are also much better in terms of sensitivity 99.82%, specificity 98.65%, and accuracy 99.89%. The deep learning‐based automated detection and grading of papilledema for clinical purposes is first effort in state of art.
Patients' Perspectives on Shared Decision‐Making About Medications in Psoriatic Arthritis: An Interview Study

Decision‐making regarding medications to manage psoriatic arthritis (PsA) is complex because of multiple disease manifestations and comorbidities. Fear of side effects from systemic medications and misalignment in priorities between patients with PsA and rheumatologists makes shared decision‐making challenging. We aimed to describe the perspectives of patients with PsA on shared decision‐making regarding medication taking.
COVID-19 Remote Consultation Services and Population in Health Inequity-Concentrating Territories: A Scoping Review

Background: This review aimed to map initiatives for measuring the satisfaction of vulnerable populations with teleconsultation services offered by public and private health care providers in their territories, during the coronavirus disease (COVID-19) pandemic. Systematic studies on the opinions of people most affected by health inequities are limited. Therefore, we included evaluations of teleconsultation-based services offered to socioeconomically disadvantaged and clinically vulnerable populations globally, with a focus on surveillance, treatment, and prevention of COVID-19. Materials and Methods: This review includes analytical and descriptive observational studies primarily from MEDLINE, EMBASE, SCOPUS, and Web of Science databases, published after the World Health Organization received the first warnings about COVID-19 from Chinese authorities in December, 2019, until December 2020. The search strategy combined aspects of COVID-19, telemedicine, patient satisfaction, and key concepts of vulnerable populations. Results: We selected 33 studies for full-text reading and 10 for critical appraisal. Two categories emerged from the qualitative analysis: telehealth evaluation and services during COVID-19, and opinions of vulnerable populations. Television and social networks play a crucial role in providing information. Although teleconsultations are practical and cost effective for patients, the majority preferred receiving in-person treatment in primary care clinics. Conclusions: Listening to the opinions of vulnerable groups and their caregivers is critical both before and during adoption of COVID-19 control measures. Health managers need to monitor the health of and delivery of services to socioeconomically and clinically vulnerable people closely, to improve services, and provide care from a human rights perspective.
Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo

Erianin is a small‐molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg−1 day−1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up‐regulated the levels of interleukin (IL)‐2 and tumor necrosis factor‐α (TNF‐α), decreased IL‐10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.
Electronic stopping power of diamond for electrons and positrons

We assess a new data set of mass electronic stopping powers of diamond for electrons and positrons. To this end, an optical energy-loss function (OELF) for this material is generated from available experimental dielectric properties of the valence band and photoabsorption mass attenuation coefficients, supplemented with a Drude-type analytical expression to interpolate at intermediate energies. From this synthetic OELF, a mean excitation energy equal to (88.5 ± 2.0) eV is extracted and the density-effect correction is evaluated using Fano’s simplified method. These quantities then allow calculating the mass electronic stopping power of diamond for electrons and positrons by means of the relativistic Bethe formula. The present results for 1 keV–1 GeV electrons in diamond are 0.9%–3.3% smaller than those corresponding to graphite as tabulated in ICRU Report 90.
Impact of microclimatic conditions and resource availability on spring and autumn phenology of temperate tree seedlings

Summary Microclimatic effects (light, temperature) are often neglected in phenological studies and little information is known about the impact of resource availability (nutrient and water) on tree’s phenological cycles. Here we experimentally studied spring and autumn phenology in four temperate trees in response to changes in bud albedo (white‐painted vs black‐painted buds), light conditions (nonshaded vs c. 70% shaded), water availability (irrigated, control and reduced precipitation) and nutrients (low vs high availability). We found that higher bud albedo or shade delayed budburst (up to +12 d), indicating that temperature is sensed locally within each bud. Leaf senescence was delayed by high nutrient availability (up to +7 d) and shade conditions (up to +39 d) in all species, except oak. Autumn phenological responses to summer droughts depended on species, with a delay for cherry (+7 d) and an advance for beech (−7 d). The strong phenological effects of bud albedo and light exposure reveal an important role of microclimatic variation on phenology. In addition to the temperature and photoperiod effects, our results suggest a tight interplay between source and sink processes in regulating the end of the seasonal vegetation cycle, which can be largely influenced by resource availability (light, water and nutrients).
Measuring research capacity development in healthcare workers: a systematic review

Objectives A key barrier in supporting health research capacity development (HRCD) is the lack of empirical measurement of competencies to assess skills and identify gaps in research activities. An effective tool to measure HRCD in healthcare workers would help inform teams to undertake more locally led research. The objective of this systematic review is to identify tools measuring healthcare workers’ individual capacities to conduct research. Design Systematic review and narrative synthesis using Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for reporting systematic reviews and narrative synthesis and the Critical Appraisals Skills Programme (CASP) checklist for qualitative studies. Data sources 11 databases were searched from inception to 16 January 2020. The first 10 pages of Google Scholar results were also screened. Eligibility criteria We included papers describing the use of tools/to measure/assess HRCD at an individual level among healthcare workers involved in research. Qualitative, mixed and quantitative methods were all eligible. Search was limited to English language only. Data extraction and synthesis Two authors independently screened and reviewed studies using Covidence software, and performed quality assessments using the extraction log validated against the CASP qualitative checklist. The content method was used to define a narrative synthesis. Results The titles and abstracts for 7474 unique records were screened and the full texts of 178 references were reviewed. 16 papers were selected: 7 quantitative studies; 1 qualitative study; 5 mixed methods studies; and 3 studies describing the creation of a tool. Tools with different levels of accuracy in measuring HRCD in healthcare workers at the individual level were described. The Research Capacity and Culture tool and the ‘Research Spider’ tool were the most commonly defined. Other tools designed for ad hoc interventions with good generalisability potential were identified. Three papers described health research core competency frameworks. All tools measured HRCD in healthcare workers at an individual level with the majority adding a measurement at the team/organisational level, or data about perceived barriers and motivators for conducting health research. Conclusions Capacity building is commonly identified with pre/postintervention evaluations without using a specific tool. This shows the need for a clear distinction between measuring the outcomes of training activities in a team/organisation, and effective actions promoting HRCD. This review highlights the lack of globally applicable comprehensive tools to provide comparable, standardised and consistent measurements of research competencies. PROSPERO registration number CRD42019122310.
Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase

ABSTRACT Supernumerary centrioles are frequently observed in diverse types of cancer cells. In this study, we investigated the mechanism underlying the generation of supernumerary centrioles during the M phase. We generated the TP53;PCNT;CEP215 triple knockout (KO) cells and determined the configurations of the centriole during the cell cycle. The triple KO cells exhibited a precocious separation of centrioles and unscheduled centriole assembly in the M phase. Supernumerary centrioles in the triple KO cells were present throughout the cell cycle; however, among all the centrioles, only two maintained an intact composition, including CEP135, CEP192, CEP295 and CEP152. Intact centrioles were formed during the S phase and the rest of the centrioles may be generated during the M phase. M-phase-assembled centrioles lacked the ability to organize microtubules in the interphase; however, a fraction of them may acquire pericentriolar material to organize microtubules during the M phase. Taken together, our work reveals the heterogeneity of the supernumerary centrioles in the triple KO cells.
Structures of Substrate Complexes of Foamy Viral Protease-Reverse Transcriptase

Reverse transcriptases (RTs) are intriguing enzymes converting single-stranded RNA to dsDNA. Their activity is essential for retroviruses, which are divided into two subfamilies differing significantly in their life cycles: Orthoretrovirinae and Spumaretrovirinae. ABSTRACT Reverse transcriptases (RTs) use their DNA polymerase and RNase H activities to catalyze the conversion of single-stranded RNA to double-stranded DNA (dsDNA), a crucial process for the replication of retroviruses. Foamy viruses (FVs) possess a unique RT, which is a fusion with the protease (PR) domain. The mechanism of substrate binding by this enzyme has been unknown. Here, we report a crystal structure of monomeric full-length marmoset FV (MFV) PR-RT in complex with an RNA/DNA hybrid substrate. We also describe a structure of MFV PR-RT with an RNase H deletion in complex with a dsDNA substrate in which the enzyme forms an asymmetric homodimer. Cryo-electron microscopy reconstruction of the full-length MFV PR-RT–dsDNA complex confirmed the dimeric architecture. These findings represent the first structural description of nucleic acid binding by a foamy viral RT and demonstrate its ability to change its oligomeric state depending on the type of bound nucleic acid. IMPORTANCE Reverse transcriptases (RTs) are intriguing enzymes converting single-stranded RNA to dsDNA. Their activity is essential for retroviruses, which are divided into two subfamilies differing significantly in their life cycles: Orthoretrovirinae and Spumaretrovirinae. The latter family is much more ancient and comprises five genera. A unique feature of foamy viral RTs is that they contain N-terminal protease (PR) domains, which are not present in orthoretroviral enzymes. So far, no structural information for full-length foamy viral PR-RT interacting with nucleic substrates has been reported. Here, we present crystal and cryo-electron microscopy structures of marmoset foamy virus (MFV) PR-RT. These structures revealed the mode of binding of RNA/DNA and dsDNA substrates. Moreover, unexpectedly, the structures and biochemical data showed that foamy viral PR-RT can adopt both a monomeric configuration, which is observed in our structures in the presence of an RNA/DNA hybrid, and an asymmetric dimer arrangement, which we observed in the presence of dsDNA.
Cordyceps sinensis aqueous extract regulates the adaptive immunity of mice subjected to 60Co γ irradiation

Cordyceps sinensis (CS) is a traditional Chinese medicine that is known for treating various diseases, and particularly for exerting therapeutic effects in immune disorders. The adaptive immunoregulatory effects of CS aqueous extract (CSAE) on γ‐irradiated mice have not been reported previously. The study aimed to evaluate the therapeutic effects of CSAE in mice immunosuppressed by irradiation. We observed that CSAE administration significantly increased body weight and spleen index, as well as the number of white blood cells, lymphocytes, and platelets in peripheral blood, T and B lymphocytes in spleen tissue, and total serum immunoglobulins in irradiated mice, whereas total serum pro‐inflammatory cytokine levels were decreased. Collectively, CSAE maintained the structural integrity of spleen tissue and repaired its damage in irradiated mice as shown by hematoxylin and eosin staining, and decreased the number of terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling‐positive splenocytes. Mechanistically, CSAE upregulated Bcl‐2, and downregulated Bax and cleaved caspase‐3 in spleen of irradiated mice. However, there were no significant differences in red blood cells and neutrophils in different groups. The results revealed that CSAE had protective effects against irradiation‐induced immunosuppression, which was likely associated with an antiapoptotic effect and the regulation of adaptive immunity.
Screening of key biomarkers and immune infiltration in Pulmonary Arterial Hypertension via integrated bioinformatics analysis

ABSTRACT This study aimed to screen key biomarkers and investigate immune infiltration in pulmonary arterial hypertension (PAH) based on integrated bioinformatics analysis. The Gene Expression Omnibus (GEO) database was used to download three mRNA expression profiles comprising 91 PAH lung specimens and 49 normal lung specimens. Three mRNA expression datasets were combined, and differentially expressed genes (DEGs) were obtained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the protein-protein interaction (PPI) network of DEGs were performed using the STRING and DAVID databases, respectively. The diagnostic value of hub gene expression in PAH was also analyzed. Finally, the infiltration of immune cells in PAH was analyzed using the CIBERSORT algorithm. Total 182 DEGs (117 upregulated and 65 downregulated) were identified, and 15 hub genes were screened. These 15 hub genes were significantly associated with immune system functions such as myeloid leukocyte migration, neutrophil migration, cell chemotaxis, Toll-like receptor signaling pathway, and NF-κB signaling pathway. A 7-gene-based model was constructed and had a better diagnostic value in identifying PAH tissues compared with normal controls. The immune infiltration profiles of the PAH and normal control samples were significantly different. High proportions of resting NK cells, activated mast cells, monocytes, and neutrophils were found in PAH samples, while high proportions of resting T cells CD4 memory and Macrophages M1 cell were found in normal control samples. Functional enrichment of DEGs and immune infiltration analysis between PAH and normal control samples might help to understand the pathogenesis of PAH.
Piezo1 channels restrain regulatory T cells but are dispensable for effector CD4+ T cell responses

Mechanosensitive Piezo1 channels restrict regulatory T cell expansion and limit disease remission in EAE. T lymphocytes encounter complex mechanical cues during an immune response. The mechanosensitive ion channel, Piezo1, drives inflammatory responses to bacterial infections, wound healing, and cancer; however, its role in helper T cell function remains unclear. In an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we found that mice with genetic deletion of Piezo1 in T cells showed diminished disease severity. Unexpectedly, Piezo1 was not essential for lymph node homing, interstitial motility, Ca2+ signaling, T cell proliferation, or differentiation into proinflammatory T helper 1 (TH1) and TH17 subsets. However, Piezo1 deletion in T cells resulted in enhanced transforming growth factor–β (TGFβ) signaling and an expanded pool of regulatory T (Treg) cells. Moreover, mice with deletion of Piezo1 specifically in Treg cells showed significant attenuation of EAE. Our results indicate that Piezo1 selectively restrains Treg cells, without influencing activation events or effector T cell functions.
Rhamnolipids enhances the growth performance through improving the immunity, intestinal barrier function and metabolome composition in broilers.

BACKGROUND Rhamnolipids (RLS), well known as a glycolipid biosurfactants, display the characteristics of low toxicity, high biodegradability, strong antibacterial properties. This study was carried out to evaluate RLS supplementation as the substitute of antibiotics effects on growth performances, immunity, intestinal barrier function and metabolome composition in broilers. RESULTS RLS treatment improved the growth performance, immunity, and intestinal barrier function in broilers. The 16S rRNA sequencing revealed that the genus Alistipes was the dominant genus in broilers treated by RLS. The UPLC-Q-TOF/MS-based metabolomics analysis indicated that the sphingolipid metabolism, glycine, serine and threonine metabolism, gycerophospholipid metabolism, and tryptophan metabolism were changed in broilers that treated by RLS. CONCLUSION L-tryptophan may be the medium for RLS to regulate the growth and physiological metabolism. RLS can be used as a potential alternative to antibiotics make potential function like antibiotics in the diet of broilers. The optimal level of supplemented RLS in the diet was 1000 mg kg-1 . This article is protected by copyright. All rights reserved.
Accurate Information from Fermentation Processes – Optimal Rate Calculation by Dynamic Window Adaptation

The calculation of metabolic turnover rates is essential for the scalable design, analysis and control of bioprocesses. A novel rate calculation algorithm is presented that is based on the dynamic adaptation of window sizes in order to deliver robust and precise rates with uniform signal-to-noise ratios. Additionally a model-based generic algorithm for deriving optimal rate calculation workflows was developed. The generic algorithms delivered more precise and accurate rates for online and offline signals, which was demonstrated for both in silico- and real batch and fed-batch fermentation process data. The presented algorithms will strongly support bioprocess development and control as enabling tools for multivariate data analysis, mechanistic modeling and dynamic experimentation.
Silver, copper and copper oxide nanoparticles in the fight against human viruses: progress and perspectives

Abstract The rapid development of nanomedicine has created a high demand for silver, copper and copper oxide nanoparticles. Due to their high reactivity and potent antimicrobial activity, silver and copper-based nanomaterials have been playing an important role in the search for new alternatives for the treatment of several issues of concern, such as pathologies caused by bacteria and viruses. Viral diseases are a significant and constant threat to public health. The most recent example is the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, the object of the present review is to highlight recent progress in the biomedical uses of these metal nanoparticles for the treatment and prevention of human viral infections. We discuss the antiviral activity of AgNPs and Cu-based NPs, including their actions against SARS-CoV-2. We also discuss the toxicity, biodistribution and excretion of AgNPs and CuNPs, along with their uses in medical devices or on inert surfaces to avoid viral dissemination by fomites. The challenges and limitations of the biomedical use of these nanoparticles are presented.