Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioinformatical and Biochemical Analyses on the Protective Role of Traditional Chinese Medicine against Age-Related Macular Degeneration

Abstract Purpose Age-related macular degeneration (AMD) is the commonest cause of permanent vision loss in the elderly. Traditional Chinese medicine (TCM) has long been used to treat AMD, although the underlying functional mechanisms are not understood. This study aims to predict the active ingredients through screening the chemical ingredients of anti-AMD decoction and to elucidate the underlying mechanisms. Methods We collected the prescriptions for effective AMD treatment with traditional Chinese medicine and screened several Chinese medicines that were used most frequently in order to compose "anti-AMD decoction. " The pharmacologically active ingredients and corresponding targets in this anti-AMD decoction were mined using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the AMD-related targets were identified through the GeneCards database. Network pharmacology was performed to construct the visual network of anti-AMD decoction-AMD protein-protein interaction (PPI). Further, the Autodock software was adopted for molecular docking on the core active ingredients and core targets. The function of core ingredients against oxidative stress and inflammation in retinal pigment epithelial cells was assessed using biochemical assays. Results We screened out 268 active ingredients in anti-AMD decoction corresponding to 258 ingredient targets, combined with 2160 disease targets in AMD, and obtained 129 drug-disease common targets. The key core proteins were predominantly involved in inflammation. Furthermore, molecular docking showed that four potential active ingredients (Quercetin, luteolin, naringenin and hederagenin) had good affinity with the core proteins, IL-6, TNF, VEGFA and MAPK3. Quercetin, luteolin and naringenin demonstrated capacities against oxidative stress and inflammation in human retinal pigment epithelial cells. Conclusions The data suggests that anti-AMD decoction has multiple functional components and targets in treating AMD, possibly mediated by suppression of oxidative stress and inflammation.
Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial

Background: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone. Methods: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non–ST-segment–elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events. Results: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3–5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613–£7015); and angiography+FFR, £4510 (£2721–£7415; P=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60–87); and angiography+FFR, 75 (interquartile range, 60–90; P=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (P=0.64). Conclusions: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT01070771.
CLASSES OF DISTRIBUTIONS APPLICABLE IN REPLACEMENT, WITH RENEWAL THEORY IMPLICATIONS,

Abstract : Age and block replacement policies are commonly used to diminish in-service failures. Unfortunately, for some items (say, those with decreasing failure rate), use of these policies may actually increase the number of in-service failures. In this paper the largest classes of life distributions are determined for which age and block replacement diminishes, either stochastically or in expected value, the number of failures in service. Bounds are obtained on survival probability, moment inequalities, and renewal quantity inequalities for distributions in these classes. It is shown that under certain reliability operations on components in a class of life distributions (such as formation of systems, addition of life lengths, and mixtures of distributions), life distributions are obtained which remain within the class. (Author)
Terahertz antenna technology for imaging applications: a technical review

Abstract The terahertz (THz) regime of the electromagnetic spectrum is rich with the emerging possibilities in imaging applications with unique characteristics to screening for weapons, explosives and bio-hazards, imaging of concealed objects, water content, and skin, and these advantages can be harnessed by using the effective THz sources and detectors. In THz imaging systems, the pulsed THz sources and detectors find unique applications and thus we have emphasized on re-visiting these kinds of systems. Several novel imaging techniques which exploit the distinctive properties of the THz systems have been presented. Moreover, the THz antenna is one of the most important components of a THz imaging system as it plays a significant role in both impedance matching and power source. Therefore, the recent developments in THz antenna design for imaging applications are reviewed and the potential challenges of such THz systems are investigated. The photoconductive antennas form the basis of many THz imaging and spectroscopy systems and finds promising applications in various scientific fields. However, for the imaging applications, there is a requirement of planar and compact THz antenna sources with on-chip fabrication and high directivity in order to achieve large depth-of-field for better image resolution. Therefore, the key modalities of improving photoconductive dipole antennas performance are identified for imaging applications. Also, the ways to improve the directivity of the photoconductive dipole antenna are discussed. The main purpose of this review is to provide an assortment of all relevant literature to bring researchers up-to-date on the current state-of-the-art and potential challenges of THz antenna technology for imaging applications.
Prescription Pathways from Initial Medication Use to Triple Therapy in Older COPD Patients: A Real-World Population Study

Abstract Background and objective Triple therapy with an inhaled corticosteroid (ICS), a long-acting β2-agonist bronchodilator (LABA) and a long-acting muscarinic antagonist (LAMA) is recommended as step-up therapy for chronic obstructive pulmonary disease (COPD) patients who continue to have persistent symptoms and increased risk of exacerbation despite treatment with dual therapy. We sought to evaluate different treatment pathways through which COPD patients were escalated to triple therapy. Methods We used population health databases from Ontario, Canada to identify individuals aged 66 or older with COPD who started triple therapy between 2014 and 2017. Median time from diagnosis to triple therapy was estimated using the Kaplan-Meier method. We classified treatment pathways based on treatments received prior to triple therapy and evaluated whether pathways differed by exacerbation history, blood eosinophil counts or time period. Results Among 4108 COPD patients initiating triple therapy, only 41.2% had a COPD exacerbation in the year prior. The three most common pathways were triple therapy as initial treatment (32.5%), LAMA to triple therapy (29.8%), and ICS + LABA to triple therapy (15.4%). Median time from diagnosis to triple therapy was 362 days (95% confidence interval:331–393 days) overall, but 14 days (95% CI 12–17 days) in the triple therapy as initial treatment pathway. This pathway was least likely to contain patients with frequent or severe exacerbations (22.0% vs. 31.5%, p < 0.001) or with blood eosinophil counts ≥300 cells/µL (18.9% vs. 22.0%, p < 0.001). Conclusion Real-world prescription of triple therapy often does not follow COPD guidelines in terms of disease severity and prior treatments attempted.
The deubiquitinating enzymes UBP12 and UBP13 positively regulate recovery after carbon starvation by modulating BES1 stability in Arabidopsis thaliana.

BRI1-EMS-SUPPRESSOR1 (BES1), a core transcription factor in the brassinosteroid (BR) signaling pathway, primarily regulates plant growth and development by influencing BR-regulated gene expression. Several E3 ubiquitin ligases regulate BES1 stability, but little is known about BES1 deubiquitination, which antagonizes E3 ligase-mediated ubiquitination to maintain BES1 homeostasis. Here, we report that two Arabidopsis thaliana deubiquitinating enzymes, UBIQUITIN-SPECIFIC PROTEASE12 (UBP12) and UBP13, interact with BES1. UBP12 and UBP13 removed ubiquitin from polyubiquitinated BES1 to stabilize both phosphorylated and dephosphorylated forms of BES1. A double mutant, ubp12-2w ubp13-3, lacking UBP12 and UBP13 function showed both BR-deficient and BR-insensitive phenotypes, whereas transgenic plants overexpressing UBP12 or UBP13 exhibited an increased BR response. Expression of UBP12 and UPB13 was induced during recovery after carbon starvation, which led to BES1 accumulation and quick recovery of stressed plants. Our work thus establishes a mechanism by which UBP12 and UBP13 regulate BES1 protein abundance to enhance BR-regulated growth during recovery after carbon starvation.
k-Sample Rank Tests for Umbrella Location-Scale Alternatives

Some rank score tests are proposed for testing the equality of all sampling distribution functions against umbrella location-scale alternatives in k-sample problem. Only the case of known peak is considered. Under the null hypothesis and a contiguous sequence of unbrella location-scale alternatives, the asymptotic properties of the proposed test statistics are investigated. Also, the asymptotic local powers are compared with each others. The results show that the tests based on the Chen-Wolfe rank analogue statistic are more powerful than others for unequally spaced umbrella location-scale alternatives and robust.
Rastreamento, Diagnóstico e Manejo da Fibrilação Atrial em Pacientes com Câncer: Evidências Atuais e Perspectivas Futuras

Resumo A fibrilação atrial (FA) é a arritmia cardíaca sustentada mais comum na população geral, tendo uma alta carga de morbimortalidade, e isso também é válido para pacientes com câncer. A associação entre FA e câncer vai ainda mais longe, com alguns estudos sugerindo que a FA pode ser um marcador de câncer oculto. Há, no entanto, uma notável escassez de dados sobre os desafios específicos do manejo da FA em pacientes com câncer. O reconhecimento e o manejo imediatos da FA nesta população especial podem diminuir a morbidade relacionada à arritmia e ter um importante benefício prognóstico. Esta revisão se concentrará nos desafios atuais de diagnóstico e manejo da FA em pacientes com câncer, com ênfase especial nas estratégias e dispositivos de rastreamento da FA e na terapia de anticoagulação com anticoagulantes orais não antagonistas da vitamina K (NOACs) para prevenção tromboembólica nesses pacientes. Alguns insights sobre as perspectivas futuras para a prevenção, diagnóstico e tratamento da FA nesta população especial também serão abordados.
LINC00657 regulate colorectal carcinoma invasion and migration by enhancing heparanase expression through recruiting SMAD family member 2

Long noncoding RNAs are master regulators of several cancer phenotypes, such as cell growth, apoptosis, and motility. This study is designed to resolve the relevance of LINC00657 with tumor invasion and migration and its action mechanism in colorectal carcinoma (CRC). LINC00657 and HPSE levels were first examined in cancerous tissues from CRC patients and CRC cells. Then functional experiments were conducted to evaluate the abilities of HCT116 and SW620 cells to proliferate, migrate, and invade when LINC00657 or HPSE was knocked down, or LINC00657 knockdown and SMAD2 overexpression were simultaneously introduced. Snail and E-cadherin levels in the CRC cells were evaluated. Next, the binding between LINC00657 and SMAD2 or between SMAD2 and HPSE was determined. LINC00657-silencing HCT116 cells were inoculated into nude mice, and the tumorigenesis and the levels of Snail and E-cadherin were evaluated. LINC00657 and HPSE were increasingly expressed in CRC. Knockdown of LINC00657 or HPSE inhibited the malignant properties of CRC cells, decreased Snail expression, and strengthened E-cadherin level. LINC00657 and HPSE could both bind to SMAD2. SMAD2 overexpression counteracted the inhibiting effect of LINC00657 silencing on HPSE expression and the growth and invasion of CRC cells. In vivo experiments further verified the suppression of LINC00657 knockdown on tumor growth and metastasis. LINC00657 recruits SMAD2 to HPSE promoter region to elevate HPSE transcription, thus accelerating CRC invasion and migration.
Molecular imprinted polymer films on RFID tags: a first step towards disposable packaging sensors

Molecular imprinted polymer (MIP) sensors offer a high potential in the development of cheap small‐scale disposable biomimetic sensors. Molecular imprinting leads to the formation of inert polymer particles with nanocavities, which can exhibit similar selectivity and specificity to target molecules as antibodies or enzymes. These sensors open up many possible applications in the field of mass‐market consumer products such as food packaging sensors. One such application is the detection of histamine in spoiled fish, which causes scombroid poisoning, a common seafood poisoning.
Hydroxypropyl Beta Cyclodextrin as a Potential Surface Modifier for Paclitaxel Nanocrystals

Paclitaxel (PTX) is a hydrophobic chemotherapeutic agent cytotoxic against many serious cancers. This study aimed at designing novel PTX nanocrystals (PTX-NCs) coated with the biocompatible and biodegradable hydroxypropyl-beta-cyclodextrin (HPβCD) polymer with specific characteristics through the formation of a non-inclusion complex. Briefly, PTX-NCs were prepared by the anti-solvent method followed by homogenization. Then, the surface of the prepared PTX-NCs was modified using the HPβCD coat (HPβCD-PTX-NCs). The prepared nanocrystals, both coated and uncoated, were characterized in terms of size, polydispersity index, charge, morphology, and stability. Moreover, the nanocrystals were investigated using powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), and Fourier transform infrared spectroscopy (FTIR). As well, the in vitro release of PTX from the nanocrystals was determined under conditions similar to the IV route of administration. Furthermore, the tendency of the nanocrystals to induce hemolysis was investigated. Results indicated that the size was about 241.4 and 310.5 nm, the polydispersity index was 0.14 and 0.21, and the zeta potential was about − 22.6 and − 16.4 mV for PTX-NCs and HPβCD-PTX-NCs, respectively. Additionally, the PXRD, FTIR, and DSC profiles can be explained by the NCs’ integrity and coat formation. The SEM images showed that both PTX-NCs and HPβCD-PTX-NCs have rod-like structures. Moreover, HPβCD-PTX-NCs had significantly superior in vitro release than both PTX-NCs and PTX. Interestingly, the hemolytic assay showed that HPβCD-PTX-NCs had a more efficient and safer profile than PTX-NCs. This study emphasized that HPβCD could be an interesting candidate for the surface modification of PTX-NCs providing superior properties such as release and safety profiles.
2-deoxy-D-glucose mitigates Citrobacter rodentium and dibenzazepine-induced gastrointestinal damage and colitis: novel implications of 2-DG polypharmacopea

Abstract Purpose Citrobacter rodentium (CR) infection coupled with blocking Notch/Wnt signaling via γ-secretase inhibitor dibenzazepine (DBZ) disrupts the gastro-intestinal (GI) barrier and induces colitis, akin to ionizing radiation (IR)-induced GI-injury. We investigated the effects of 2-deoxy-D-glucose (2-DG) to ameliorate the CR-DBZ-induced GI damage. Materials and methods NIH:Swiss outbred mice were inoculated with 109CFUs of CR orally. DBZ was administered intraperitoneally (10 μM/kg b.wt; for 10 days 2 days post-CR infection). Mice were fed with 0.4% 2-DG (w/v) daily in drinking water. For microbiota depletion, antibiotics (Abx), 1 g/l metronidazole, and 0.2 g/l ciprofloxacin were administered for 10 days in drinking water. Oxidative stress, survival assay, colonic crypt hyperplasia, Notch/Wnt downstream signaling, immunomodulation, and bacterial dysbiosis were measured. Results We show that real-time visualization of reactive oxygen species (ROS) is similar during CR-induced colonic infection and IR-induced GI-damage. The histology revealed that dietary 2-DG mitigates CR + DBZ-induced colitis and improves survival compared with CR + DBZ alone. These changes were phenocopied in Abx-treated mice. Both 2-DG and Abx reduced dysbiosis, increased proliferation, inhibited pro-inflammatory response, and restored Hes-1 and β-catenin protein levels, in the crypts. Conclusion The energy disruptor 2-DG mitigates bacterial infection and its responsive hyperplasia/colitis, indicating its utility as a mitigator of infection/IR-induced GI-damage.
Observation of Cyclosporin A: Sustained Release Intraocular Lens Implantation in Rabbit Eyes

Abstract Purpose To observe the performance of cyclosporine A (CsA)-loaded intraocular lens (IOLs) implanted into rabbit eyes. Methods To prepare a PLGA-based CsA-sustained release IOLs and study the in vitro drug release. Forty-two New Zealand white rabbits were randomly and equally divided into three groups, and all right eyes underwent phacoemulsification. In group A, a common polymethylmethacrylate (PMMA) IOLs was implanted, while polylactide-glycoli acid (PLGA-loaded)-PMMA-IOLs was implanted in group B, and CsA-PLGA-PMMA-IOLs was implanted in group C. All experimental eyes were examined by slit-lamp microscopy. In addition, fundoscopy and the number of corneal endothelial cells, anterior chamber flare grading, and the number of aqueous humor cells were assessed at different time points post-surgery. The wet lens capsule was weighed and histological examination was performed 6 months post-operation. Results In the early post-operative period, the inflammatory reaction of anterior chamber in groups A and B were more severe than group C. The initial appearance of PCO in group C was much later than the other two groups (F = 68.91; p = 0.000), and PCO grade in group C was much lower than the other two groups (χ2 = 36.07; p = 0.000). The mean weights of wet lens capsules in groups A and B were significantly heavier than group C (F = 134.88; p = 0.00). Histological observation showed no obvious toxic reaction in the intraocular tissues of the CsA-PLGA-PMMA-IOLs group, and the proliferation and accumulation of lens epithelial cells in groups A and B were greater than in group C. Conclusion CsA-sustained release IOLs can effectively prevent PCO in rabbit eyes without defined intraocular toxicity.
Investigating the inflammatory status in the patients candidate for second angiography after coronary stent implantation

Abstract Background Inflammation has been shown to be an important feature of atherosclerosis. We aimed to assess a profile of inflammatory cytokines and growth factors in patients with established coronary artery disease (CAD), 12 months after stent implantation. Methods A total of 193 patients with CAD, who were candidates for angiography, 12 months after stent implantation (cases), were compared with 107 patients with CAD, who were candidates for their first angiography (controls). Fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) were measured using routine methods. The serum concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF and VEGF were determined using competitive chemiluminescence immunoassays. Results Serum levels of FBG (p = .002), TG (p = .029) and hs-CRP (p = .005) were significantly lower in cases than controls. The cytokines and growth factor profiles in cases were significantly different from controls. After multivariate analysis, serum levels of IL-2 (p < .001), IL-4 (p = .028) were significantly lower in cases compared with the controls while serum levels of IL-8, TNF-α, MCP-1, EGF and VEGF were significantly higher in the cases (p < .001). Conclusions In patients with CAD and higher consumption of drug used (statins, aspirin and glucose lowering agents) to mitigate the risk of a secondary event, the level of hs-CRP one year after stent implantation decreased despite of significant higher serum levels of pro- and anti-inflammatory cytokines and growth factors.
Chloroplast redox state changes mark cell‐to‐cell signaling in the hypersensitive response

Summary Hypersensitive response (HR)‐conferred resistance is associated with induction of programmed cell death and pathogen spread restriction in its proximity. The exact role of chloroplastic reactive oxygen species and its link with salicylic acid (SA) signaling in HR remain unexplained. To unravel this, we performed a detailed spatiotemporal analysis of chloroplast redox response in palisade mesophyll and upper epidermis to potato virus Y (PVY) infection in a resistant potato genotype and its transgenic counterpart with impaired SA accumulation and compromised resistance. Besides the cells close to the cell death zone, we detected individual cells with oxidized chloroplasts further from the cell death zone. These are rare in SA‐deficient plants, suggesting their role in signaling for resistance. We confirmed that chloroplast redox changes play important roles in signaling for resistance, as blocking chloroplast redox changes affected spatial responses at the transcriptional level. Through spatiotemporal study of stromule induction after PVY infection, we show that stromules are induced by cell death and also as a response to PVY multiplication at the front of infection. Overall induction of stromules is attenuated in SA‐deficient plants.