Miracle-dz/UniFAR-FTUs huggingface dataset:
A sophisticated case of division of labour in the trimorphic stamens of the Cassia fistula (Leguminosae) flower

Abstract Buzz-pollinated pollen flowers have pollen as the primary resource for pollinators and must deal with a conflict between the exploitation of pollen grains by bees and pollination success. It has been hypothesized that heterostemony allows division of labour between stamens as a solution to the pollen dilemma. To test the division of labour hypothesis, we chose Cassia fistula, which has a trimorphic androecium and analysed androecium development, pollen grain release mechanisms and visitor behaviour. We explored the reflectance of floral organs and carried out an exclusion experiment to test the attractiveness of each stamen morph to the bee species. Finally, we explored the structural, ultrastructural and functional variation between the pollen grains, including pollen viability across stamen morphs. The differences among the three stamen morphs, which is developed from two whorls of the stamen, are the first evidence of the division of labour in our study system. Large Bombus and Xylocopa bees actively and exclusively exploited the pollen grains from the central poricidal anthers generating pollen deposition on their bodies. The reflectance pattern of floral organs indicated a targeting of these large bees to the central anthers, corroborated by the anther manipulative experiment where only the exclusion of the anthers positioned in the flower centre, especially the intermediate stamens, reduced bee visits. Both results revealed a division of labour, in which the intermediate stamen morph was responsible for both floral attractiveness and pollen resources. Only the largest stamen morph produced germinable pollen grains, highlighting their role as pollinating stamens. The smallest stamen morph has a less clear function, likely representing an economy in pollen production for feeding function. Our findings suggest that the evolution of the trimorphic androecium is associated with division of labour in large pollen flowers and can represent a strong strategy for circumventing the pollen dilemma, optimizing the feeding function by reducing pollen grain investment from central anthers.
Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells

COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, therapeutics that can help manage the disease are still required until immunity has been achieved globally. The identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in-line with reported proteinuria and liver damage in patients with COVID-19. Using the nano-luciferase as a measure of virus replication we identified 35 drugs that reduced replication in Vero cells and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.
Agreement Between Self-Reported Information and Administrative Data on Comorbidities, Imaging and Treatment in Denmark – A Validation Study of 38,745 Patients with Knee or Hip Osteoarthritis

Purpose To validate self-reported information obtained from patients with knee or hip osteoarthritis (OA) in primary care against administrative data from the three national Danish registries. Patients and Methods We compared the baseline and 12-month follow-up data from 38,745 patients with knee or hip OA participating in the Good Life with osteoArthritis in Denmark (GLA:D®) program with registry-based data on joint surgeries, pain medication dispensing, radiographs, and hospital diagnoses. Agreement was calculated using Cohen’s Kappa (k) and percentage agreement, both with 95% CI. Results There was a moderate agreement between self-report and registry-based data for previous knee surgery (k=0.58, 84.99%) and a substantial agreement for previous hip surgery (k=0.73, 97.05%). Agreement varied from 0.05 to 0.95 and 84.99% to 99.94% for different types of surgeries with lowest agreement for collateral ligament surgery (k=0.05, 99.82%) and highest agreement for joint replacement (k=0.95, 99.54% for knee; k=0.95, 99.48% for hip). There was a moderate agreement (k=0.41, 81.59%) for knee and a slight agreement (k=0.20, 64.79%) for hip radiographs. Agreement varied from 0.01 to 0.53 and 65.39% to 99.90% for pain medication with lowest agreement for topical NSAID (k=0.01, 95.00%) and highest agreement for opioids (k=0.53, 92.56%). For comorbidities, agreement varied from 0.14 to 0.90 and 78.07% to 98.91%, with lowest agreement for anemia or other blood disease (k=0.14, 97.63%) and highest agreement for diabetes (k=0.90, 98.73%). Conclusion As the most common types of pain medication used by patients with OA can be bought over-the-counter and as most OA patients are treated in primary care, which is often not covered by national registries, self-report of pain medication use and comorbidities is preferred but cannot be sufficiently validated against registry-based data. Future studies collecting self-reported information on joint surgery and pain medication from patients with OA should use a less detailed categorization to improve accuracy.
Comparative study of subdural drain (SDD) versus sub periosteal drain (SPD) in treating patient with chronic subdural hematoma (CSDH)

Background: Chronic subdural hematoma (CSDH) is common neurosurgical condition encountered in daily practice. Burr holes evacuation is standard treatment for symptomatic cases. Both subdural drain (SDD) and subperiosteal drain (SPD) have been reported to lower the recurrence rate when used in conjunction with burr holes. A randomized controlled trials were done to see if there were any differences in clinical and radiographic outcomes between the two types of drains. Methods: A total of 42 CSDH patients were enrolled and allocated to one of two groups: SDD (n = 21) or SPD (n = 21). Demographic data, perioperative imaging characteristics, clinical outcome, and recurrence rate were recorded for comparison. Results: In both groups, demographic characteristics such as sex ratio, mean age of patients, concomitant disease, and antithrombotic agent use were similar. At 6 months, 20 (95.2%) and 21 (100%) cases in the SDD and SPD groups, respectively, had a favorable outcome (mRS 0–3). Complete hematoma resolution at 6 months was achieved in 21 (100%) and 19 (90.5%) cases of the SDD and SPD groups, respectively. The amount of drain within 48 h was not difference between the two groups. None of the SDD recurred, but two of the SPD group did, necessitating reoperation, which had no effect on the final outcome. Conclusion: These findings indicate that the drain type (SDD or SPD) has no effect on the outcome. The surgeon’s preference determines which procedure is used. Except in symptomatic circumstances, routine postoperative imaging may not be required.
The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation

Many important bacterial pathogens are using the type III secretion system to deliver effectors into host cells. Salmonella Typhimurium (S. Typhimurium) is a pathogenic Gram-negative bacterium with the type III secretion system as its major virulence factor. Our previous studies demonstrated that thymol, a monoterpene phenol derivative of cymene, inhibited S. Typhimurium invasion into mammalian cells and protected mice from infection. However, the antibacterial mechanism of thymol is not clear. In this study, we revealed that thymol interferes with the abundance of about 100 bacterial proteins through proteomic analysis. Among the 42 proteins whose abundance was reduced, 11 were important virulence factors associated with T3SS-1. Further analyses with SipA revealed that thymol directly interacts with this protein to induce conformational changes, which makes it susceptible to the Lon protease. In agreement with this observation, thymol effectively blocks cell invasion by S. Typhimurium. Thus, thymol represents a class of anti-virulence compounds that function by targeting pathogenic factors for degradation.
Magnetite Fe3O4 Nanoparticles Enhance Mild Microwave Ablation of Tumor by Activating the IRE1-ASK1-JNK Pathway and Inducing Endoplasmic Reticulum Stress

Purpose With the development of nanomedicine, microwave ablation enhanced by multifunctional nanoplatforms has been widely studied for synergistic cancer therapy. Though scientists have got a lot of significant achievements in this field, the detailed molecular mechanisms and potential targets of microwave ablation enhanced by multifunctional nanoplatforms still need further exploration. In this study, we found that a kind of magnetite Fe3O4 nanoparticles (Fe3O4 NPs) could induce severe endoplasmic reticulum stress and activate cancer apoptosis under the irradiation of mild microwave. Methods In this study, plenty of studies including cell immunofluorescence, mitochondrial membrane potential, electron microscopy, atomic force microscopy and microwave ablation in vivo were conducted to explore the molecular mechanisms and potential targets of microwave ablation enhanced by the Fe3O4 NPs. Results The IRE1-ASK1-JNK pathway was strongly activated in A375 cells treated with both Fe3O4 NPs and mild microwave. The endoplasmic reticulum of the A375 cells was significantly dilated and exhibited ballooning degeneration. By investigating the mitochondrial membrane potential (ΔΨm), we found that the mitochondria of cancer cells had been significantly damaged under microwave treatment coupled with Fe3O4 NPs. In addition, melanoma of B16F10-bearing mice had also been effectively inhibited after being treated with Fe3O4 NPs and microwave. Conclusion In this study, we found that a kind of magnetite Fe3O4 nanoparticles could induce severe ER stress and activate cancer apoptosis under mild microwave irradiation. Apparent apoptosis had been observed in the A375 cells under a scanning electron microscope and transmission electron microscope. Moreover, melanoma had also been inhibited effectively in vivo. As a result, the endoplasmic reticulum stress is a promising target with clinical potential in nanomedicine and cancer therapy.
How do befriending interventions alleviate loneliness and social isolation among older people? A realist evaluation study

Background Befriending is a popular way in which to intervene to combat loneliness and social isolation among older people. However, there is a need to improve our understanding about how these interventions work, for whom and in which contexts, to make the best use of the increasing investment in the provision and delivery of befriending services. Methods A realist evaluation was undertaken as it focuses on uncovering causal processes and interactions between mechanisms and contextual characteristics. Five case studies of befriending programmes in Northern Ireland were studied, reflecting variation in contextual variables, service user and provider characteristics. Data was collected via service documentation and semi-structured interviews (n = 46) with stakeholders involved in the delivery and receipt of befriending interventions. Results Eight initial programme theories were generated, which were ‘tested’ in the case study analysis to uncover context-mechanism-outcome relationships. Mechanisms identified included reciprocity, empathy, autonomy, and privacy which were triggered in different contexts to support the alleviation of loneliness and social isolation. Reciprocity was ‘triggered’ in contexts where service users and befrienders shared characteristics, the befriender was a volunteer and befriending took the form of physical companionship. Contexts characterised in terms of shared experiences between befriender and service user triggered empathy. Autonomy was triggered in contexts where befriending relationships were delivered long-term and did not focus on a pre-defined set of priorities. Privacy was triggered in contexts where service users had a cognitive/sensory impairment and received one-to-one delivery. Conclusion This study improves understanding about how and why befriending interventions work. Findings indicate that services should be tailored to the needs of service users and take into consideration characteristics including mobility, impairments e.g. physical, sensory and/or cognitive, as well as the influence of service characteristics including payment for befrienders, fixed/long-term befriending relationship, one-to-one support and the impact of non-verbal communication via face-to-face delivery.
Comparative Analyses of Liquid-Biopsy MicroRNA371a-3p Isolation Protocols for Serum and Plasma

Simple Summary The active disease status of patients with a malignant germ cell tumor can be evaluated using detection of specific body-circulating microRNAs. However, various methods are reported to isolate and detect microRNAs from blood, possibly influencing the score as positive or negative. Here, we investigated two frequently used techniques for microRNA isolation from blood, either serum or plasma, to evaluate possible differences. These data are required to compare published studies and to select the best methods in the future. No effect of either starting with plasma or serum was found, indicating that both blood products can be used. The bead-based method was more stable and applicable on small blood volumes, whereas the total RNA method exhibited a higher sensitivity due to a larger starting volume. These results are important to develop the optimal method for the detection of microRNAs in blood to monitor malignant germ cell tumor patients in clinic practice. Abstract MicroRNAs (miRNAs) are short, non-coding RNAs involved in translation regulation. Dysregulation has been identified in cancer cells. miRNAs can be secreted and detectable in body fluids; therefore, they are potential liquid-biopsy biomarkers. The miR-371a-3 cluster members are an example, monitoring the presence of malignant germ cell tumors based on patient serum/plasma analyses. However, a large variety of isolation techniques on sample types (serum vs. plasma) are reported, hampering interstudy comparisons. Therefore, we analyzed the impact of using the miRNeasy Serum/Plasma Kit (cell-free total RNA purification) Qiagen extraction kit and the TaqMan anti-miRNA bead-capture procedure of ThermoFisher for miRNA isolation. Ten normal male matched serum and plasma samples and seventeen testicular germ cell tumor patient serum samples were investigated. The Qiagen kit requires a higher input volume (200 µL vs. 50 µL), resulting in higher sensitivity. Serum and plasma comparison demonstrated high similarity in miRNA levels. Titration experiments showed that the bead-capture procedure is superior in cases of lower starting volumes (<100 µL). This study highlights the strengths and limitations of two different isolation protocols, relevant for in vivo analysis with small starting volumes. In summary, miRNA detection levels results varied little between plasma and serum, whereas for low volumes the bead capture isolation method is preferable.
A novel and efficient deep learning approach for COVID‐19 detection using X‐ray imaging modality

With the exponential growth of COVID‐19 cases, medical practitioners are searching for accurate and quick automated detection methods to prevent Covid from spreading while trying to reduce the computational requirement of devices. In this research article, a deep learning Convolutional Neural Network (CNN) based accurate and efficient ensemble model using deep learning is being proposed with 2161 COVID‐19, 2022 pneumonia, and 5863 normal chest X‐ray images that has been collected from previous publications and other online resources. To improve the detection accuracy contrast enhancement and image normalization have been done to produce better quality images at the pre‐processing level. Further data augmentation methods are used by creating modified versions of images in the dataset to train the four efficient CNN models (Inceptionv3, DenseNet121, Xception, InceptionResNetv2) Experimental results provide 98.33% accuracy for binary class and 92.36% for multiclass. The performance evaluation metrics reveal that this tool can be very helpful for early disease diagnosis.
The Association of Morning Hypertension With Target Organ Damage in Patients With Chronic Kidney Disease and Hypertension

Objectives: To determine the association between morning hypertension and target organ damage (TOD) in patients with chronic kidney disease (CKD) and hypertension. Methods: In this cross-sectional study, 447 patients with CKD and hypertension from two centers were enrolled. Ambulatory blood pressure monitoring was conducted in all patients. Linear regression and logistic regression analysis were used to determine the association between morning hypertension and TOD in patients with CKD and hypertension, including assessments of estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), urine protein/creatinine ratio (UPCR), and left ventricular hypertrophy (LVH). Results: Overall, 194 (43.4%) participants had morning hypertension. Morning hypertension was strongly correlated with LVH [odds ratio (OR), 2.14; 95% confidence interval (CI), 1.3–3.51; p < 0.01], lower level of eGFR (β = −0.51; 95%CI, −0.95–−0.08; p < 0.05), higher LVMI (β = 0.06; 95%CI, 0.04–0.08, p < 0.001), and UPCR (β = 0.22; 95%CI, 0.06–0.38, p < 0.01), independent of nocturnal hypertension and elevated morning blood pressure surge. As a continuous variable, both morning systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found to be associated with LVH and higher level of UPCR and LVMI (p < 0.05), whereas only morning SBP was negatively correlated with eGFR (p < 0.01). Conclusion: Morning hypertension was strongly correlated with cardiac damage and impaired kidney function in CKD patients with hypertension, independent of nocturnal hypertension and morning surge in blood pressure. Morning hypertension in CKD patients warrants further attention.
Alzheimer’s Disease Progressively Reduces Visual Functional Network Connectivity

Background: Postmortem studies of brains with Alzheimer’s disease (AD) not only find amyloid-beta (Aβ) and neurofibrillary tangles (NFT) in the visual cortex, but also reveal temporally sequential changes in AD pathology from higher-order association areas to lower-order areas and then primary visual area (V1) with disease progression. Objective: This study investigated the effect of AD severity on visual functional network. Methods: Eight severe AD (SAD) patients, 11 mild/moderate AD (MAD), and 26 healthy senior (HS) controls undertook a resting-state fMRI (rs-fMRI) and a task fMRI of viewing face photos. A resting-state visual functional connectivity (FC) network and a face-evoked visual-processing network were identified for each group. Results: For the HS, the identified group-mean face-evoked visual-processing network in the ventral pathway started from V1 and ended within the fusiform gyrus. In contrast, the resting-state visual FC network was mainly confined within the visual cortex. AD disrupted these two functional networks in a similar severity dependent manner: the more severe the cognitive impairment, the greater reduction in network connectivity. For the face-evoked visual-processing network, MAD disrupted and reduced activation mainly in the higher-order visual association areas, with SAD further disrupting and reducing activation in the lower-order areas. Conclusion: These findings provide a functional corollary to the canonical view of the temporally sequential advancement of AD pathology through visual cortical areas. The association of the disruption of functional networks, especially the face-evoked visual-processing network, with AD severity suggests a potential predictor or biomarker of AD progression.
ESPL1 Is a Novel Prognostic Biomarker Associated With the Malignant Features of Glioma

Research has confirmed that extra spindle pole bodies-like 1 (ESPL1), an etiological factor, promotes the malignant progression of cancers. However, the relationship between ESPL1 and glioma has not yet been demonstrated. The purpose of this study was to reveal the potential mechanisms of ESPL1-mediated malignant glioma progression. Gene expression data and detailed clinical information of glioma cases were obtained from multiple public databases. Subsequently, a series of bioinformatics analyses were used to elucidate the effects of ESPL1 on glioma. The results demonstrated that the mRNA and protein levels of ESPL1 in glioma were higher than those in normal brain tissues. In addition, ESPL1 expression was considerably associated with the clinical and pathological features of gliomas, such as World Health Organization grade, histology, and 1p19q co-deletion status. Importantly, ESPL1 reduced the overall survival (OS) of glioma patients and had prognostic value for gliomas. Gene set enrichment analysis (GSEA) indirectly revealed that ESPL1 regulates the activation of cancer-related pathways, such as the cell cycle and base excision repair pathways. In addition, we used the Connectivity Map (CMap) database to screen three molecular drugs that inhibit ESPL1: thioguanosine, antimycin A, and zidovudine. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of ESPL1 in glioma cell lines. This study plays an important role in revealing the etiology of glioma by revealing the function of ESPL1, providing a potential molecular marker for the diagnosis and treatment of glioma, especially low-grade glioma.
Photocrosslinking silver nanoparticles–aloe vera–silk fibroin composite hydrogel for treatment of full-thickness cutaneous wounds

Abstract Damage to the skin causes physiological and functional issues. The most effective treatment approach is the use of wound dressings. Silk fibroin (SF) is a promising candidate biomaterial for regulating wound healing; however, its antibacterial properties and biological activity must be further improved. In this study, a photocrosslinking hydrogel was developed to treat full-thickness cutaneous wounds. The composite hydrogel (Ag–AV–SF hydrogel) was prepared by introducing the silver nanoparticles (AgNPs) and aloe vera (AV) as the modifiers. In vitro study exhibited great antibacterial ability, biocompatibility and cell-proliferation and -migration-promoting capacities. It also showed the pH-response releasing properties which release more AgNPs in a simulated chronic infection environment. The healing effect evaluation in vivo showed the healing-promoting ability of the Ag–AV–SF hydrogel was stronger than the single-modifiers groups, and the healing rate of it reached 97.02% on Day 21, higher than the commercial wound dressing, silver sulfadiazine (SS) cream on sale. Additionally, the histological and protein expression results showed that the Ag–AV–SF hydrogel has a greater effect on the pro-healing regenerative phenotype with M2 macrophages at the early stage, reconstructing the blood vessels networks and inhibiting the formation of scars. In summary, the Ag–AV–SF hydrogel developed in this study had good physical properties, overwhelming antibacterial properties, satisfactory biocompatibility and significantly promoting effect on cell proliferation, migration and wound healing. Overall, our results suggest that the Ag–AV–SF hydrogel we developed has great potential for improving the wound healing in clinical treatment.