Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclopentanone Derivative Attenuates Memory Impairment by Inhibiting Amyloid Plaques Formation in the 5xFAD Mice

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder. This study was designed to investigate the effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) on behavior, amyloid β (Aβ) plaque deposition, and βAPP cleaving enzyme-1 (BACE-1) expression in the 5xFAD mouse brain. In this study, computational studies were conducted to predict the binding mode of the 3NCP with target sites of the β-secretase. In vivo studies were performed on the 5xFAD mice model of AD using different behavioral test models like light/dark box, elevated plus maze (EPM), and the Barnes maze tests for the assessment of anxiety, spatial learning and memory. The thioflavin-S staining, immunohistochemistry (IHC), and RT-PCR studies were carried out to find the effect of the 3NCP on the β-amyloid plaques formation and BACE-1 expression. The results of the computational studies showed that the 3NCP has excellent binding affinities for beta-secretase. The light/dark box study depicted that the 3NCP does not cause anxiety. The 3NCP treatment effects in the EPM and Barnes maze tests showed a significant effect on learning and memory. Furthermore, the results of the thioflavin staining and IHC revealed that the 3NCP significantly reduced the formation of the beta-amyloid plaques in brain tissues. Moreover, the RT-PCR study showed that 3NCP significantly reduced the BACE-1 expression in the brain. Conclusively, the results of the current study demonstrate that the 3NCP may be a potential candidate for AD treatment in the future.
Increasing Angiogenesis Factors in Hypoxic Diabetic Wound Conditions by siRNA Delivery: Additive Effect of LbL-Gold Nanocarriers and Desloratadine-Induced Lysosomal Escape

Impaired wound healing in people with diabetes has multifactorial causes, with insufficient neovascularization being one of the most important. Hypoxia-inducible factor-1 (HIF-1) plays a central role in the hypoxia-induced response by activating angiogenesis factors. As its activity is under precise regulatory control of prolyl-hydroxylase domain 2 (PHD-2), downregulation of PHD-2 by small interfering RNA (siRNA) could stabilize HIF-1α and, therefore, upregulate the expression of pro-angiogenic factors as well. Intracellular delivery of siRNA can be achieved with nanocarriers that must fulfill several requirements, including high stability, low toxicity, and high transfection efficiency. Here, we designed and compared the performance of layer-by-layer self-assembled siRNA-loaded gold nanoparticles with two different outer layers—Chitosan (AuNP@CS) and Poly L-arginine (AuNP@PLA). Although both formulations have exactly the same core, we find that a PLA outer layer improves the endosomal escape of siRNA, and therefore, transfection efficiency, after endocytic uptake in NIH-3T3 cells. Furthermore, we found that endosomal escape of AuNP@PLA could be improved further when cells were additionally treated with desloratadine, thus outperforming commercial reagents such as Lipofectamine® and jetPRIME®. AuNP@PLA in combination with desloratadine was proven to induce PHD-2 silencing in fibroblasts, allowing upregulation of pro-angiogenic pathways. This finding in an in vitro context constitutes a first step towards improving diabetic wound healing with siRNA therapy.
One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA)

Simple Summary One-step nucleic acid amplification (OSNA) is an automated molecular diagnostic assay used to detect metastases by analyzing the levels of cytokeratin 19 mRNA in whole lymph nodes. It has been validated as an accurate and reliable tool for staging in several types of cancers and is included in the National Institute for Health and Care Excellence guidelines for the management of breast cancer. ENDO-OSNA is a large, observational, multicenter study designed to evaluate the efficacy of OSNA for the detection of sentinel lymph node (SLN) metastasis in patients with early-stage endometrial cancer. We found that the OSNA assay shows higher sensitivity, specificity, and diagnostic accuracy in the detection of SLN metastasis, including low-volume metastasis, compared to standard pathological ultrastaging. Moreover, OSNA could aid in the identification of patients with intermediate or high-risk endometrial cancer, and lead to treatment decisions that could improve their prognosis. Abstract The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.
Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study

Type 2 diabetes (T2D) represents one of the major health issues of this century. Despite the availability of an increasing number of anti-hyperglycemic drugs, a significant proportion of patients are inadequately controlled, thus highlighting the need for novel biomarkers to guide treatment selection. MicroRNAs (miRNAs) are small non-coding RNAs, proposed as useful diagnostic/prognostic markers. The aim of our study was to identify a miRNA signature occurring in responders to glucagon-like peptide 1 receptor agonists (GLP1-RA) therapy. We investigated the expression profile of eight T2D-associated circulating miRNAs in 26 prospectively evaluated diabetic patients in whom GLP1-RA was added to metformin. As expected, GLP1-RA treatment induced significant reductions of HbA1c and body weight, both after 6 and 12 months of therapy. Of note, baseline expression levels of the selected miRNAs revealed two distinct patient clusters: “high expressing” and “low expressing”. Interestingly, a significantly higher percentage of patients in the high expression group reached the glycemic target after 12 months of treatment. Our findings suggest that the evaluation of miRNA expression could be used to predict the likelihood of an early treatment response to GLP1-RA and to select patients in whom to start such treatment, paving the way to a personalized medicine approach.
Comparison of Experiences in Two Birth Cohorts Comprising Young Families with Children under Four Years during the Initial COVID-19 Lockdown in Australia and the UK: A Qualitative Study

This study aims to understand the experience and impact of the initial COVID-19 lockdown in young families with children aged below 4 years. Free text questions were administered to participants in the ORIGINS (Australia) and Born in Bradford (UK) cohort studies to collect qualitative information on worries, concerns and enjoyable experiences during the pandemic. A total of 903 (400 for ORIGINS and 503 for BiB) participants completed the two surveys during April 2020. Despite varying in geography, levels of socio-economic disadvantage and their situational context during the pandemic, respondents from both cohorts reported similar worries and challenges during the lockdown period, including: employment/finances, health anxiety, mental health and social isolation, caring for children and child development. Families across the globe experienced both positive and negative immediate impacts of COVID-19. Population-based data can be used to inform the development of support services, public health campaigns and universal interventions to assist families in future health crises.
Analysis of Tweets Containing Information Related to Rheumatological Diseases on Twitter

Background: Tweets often indicate the interests of Twitter users. Data from Twitter could be used to better understand the interest in and perceptions of a variety of diseases and medical conditions, including rheumatological diseases which have increased in prevalence over the past several decades. The aim of this study was to perform a content analysis of tweets referring to rheumatological diseases. Methods: The content of each tweet was rated as medical (including a reference to diagnosis, treatment, or other aspects of the disease) or non-medical (such as requesting help). The type of user and the suitability of the medical content (appropriate content or, on the contrary, fake content if it was medically inappropriate according to the current medical knowledge) were also evaluated. The number of retweets and likes generated were also investigated. Results: We analyzed a total of 1514 tweets: 1093 classified as medical and 421 as non-medical. The diseases with more tweets were the most prevalent. Within the medical tweets, the content of these varied according to the disease (some more focused on diagnosis and others on treatment). The fake content came from unidentified users and mostly referred to the treatment of diseases. Conclusions: According to our results, the analysis of content posted on Twitter in regard to rheumatological diseases may be useful for investigating the public’s prevailing areas of interest, concerns and opinions. Thus, it could facilitate communication between health care professionals and patients, and ultimately improve the doctor–patient relationship. Due to the interest shown in medical issues it seems desirable to have healthcare institutions and healthcare workers involved in Twitter.
Study on Concrete Deterioration in Different NaCl-Na2SO4 Solutions and the Mechanism of Cl− Diffusion

The diffusion of sulfate (SO42−) and chloride (Cl−) ions from rivers, salt lakes and saline soil into reinforced concrete is one of the main factors that contributes to the corrosion of steel reinforcing bars, thus reducing their mechanical properties. This work experimentally investigated the corrosion process involving various concentrations of NaCl-Na2SO4 leading to the coupled erosion of concrete. The appearance, weight, and mechanical properties of the concrete were measured throughout the erosion process, and the Cl− and SO42− contents in concrete were determined using Cl− rapid testing and spectrophotometry, respectively. Scanning electron microscopy, energy spectrometry, X-ray diffractometry, and mercury porosimetry were also employed to analyze microstructural changes and complex mineral combinations in these samples. The results showed that with higher Na2SO4 concentration and longer exposure time, the mass, compressive strength, and relative dynamic elastic modulus gradually increased and large pores gradually transitioned to medium and small pores. When the Na2SO4 mass fraction in the salt solution was ≥10 wt%, there was a downward trend in the mechanical properties after exposure for a certain period of time. The Cl− diffusion rate was thus related to Na2SO4 concentration. When the Na2SO4 mass fraction in solution was ≤5 wt% and exposure time short, SO42− and cement hydration/corrosion products hindered Cl− migration. In a concentrated Na2SO4 environment (≥10 wt%), the Cl− diffusion rate was accelerated in the later stages of exposure. These experiments further revealed that the Cl− migration rate was higher than that of SO42−.
Impact of Economic Development Level and Agricultural Water Use on Agricultural Production Scale in China

The change of agricultural production scale is directly related to food security and the stable development of social economy. Particularly, the influence of economic development level and agricultural water use on agricultural production scale cannot be ignored. Therefore, this paper uses the fully modified ordinary least squares (FMOLS) and the Dumitrescu–Hurlin panel causality test models to discuss the effects of the level of economic development, agricultural water use, the level of urbanization, and the market price of agricultural products on the scale of agricultural production in China. The analysis results indicated that agricultural water use, the level of urbanization, and the market price of agricultural products promoted an increase of the scale of agricultural production at the total sample level; a 1% increase for these three variables will result in an increase of the scale of agricultural production of 0.634%, 0.377%, and 0.292%, respectively. The influence of economic development level on agricultural production scale accords with Kuznets curve. However, at the regional level, the influence of each variable on the eastern region is consistent with the trend of the total sample. In the central region, the impact of economic development on agricultural production scale shows a U-shaped curve, and the improvement of urbanization level inhibits the expansion of agricultural production scale. In the western region, all variables failed to pass the significance test. The results of the FMOLS model were validated by the fixed effects model. The results of causality tests showed that bidirectional causality existed between the scale of agricultural production and the level of economic development, the scale of agricultural production and agricultural water use, the level of economic development and the market price of agricultural products, and the level of urbanization and the market price of agricultural products. In different regions, there were differences in causality between variables. Therefore, based on the empirical results, we put forward some policy suggestions to maintain the scale of agricultural production.
Relationship between Green and Blue Spaces with Mental and Physical Health: A Systematic Review of Longitudinal Observational Studies

There is growing interest in the ways natural environments influence the development and progression of long-term health conditions. Vegetation and water bodies, also known as green and blue spaces, have the potential to affect health and behaviour through the provision of aesthetic spaces for relaxation, socialisation and physical activity. While research has previously assessed how green and blue spaces affect mental and physical wellbeing, little is known about the relationship between these exposures and health outcomes over time. This systematic review summarised the published evidence from longitudinal observational studies on the relationship between exposure to green and blue space with mental and physical health in adults. Included health outcomes were common mental health conditions, severe mental health conditions and noncommunicable diseases (NCDs). An online bibliographic search of six databases was completed in July 2020. After title, abstract and full-text screening, 44 eligible studies were included in the analysis. Depression, diabetes and obesity were the health conditions most frequently studied in longitudinal relationships. The majority of exposures included indicators of green space availability and urban green space accessibility. Few studies addressed the relationship between blue space and health. The narrative synthesis pointed towards mixed evidence of a protective relationship between exposure to green space and health. There was high heterogeneity in exposure measures and adjustment for confounding between studies. Future policy and research should seek a standardised approach towards measuring green and blue space exposures and employ theoretical grounds for confounder adjustment.
Shorter Axial Length Is a Risk Factor for Proliferative Vitreoretinopathy Grade C in Eyes Unmodified by Surgical Invasion

Purpose: To investigate the risk factors for the development of proliferative vitreoretinopathy grade C (PVR-C), independent of prior surgical invasion. Methods: Patients who underwent surgery for rhegmatogenous retinal detachment were prospectively registered with the Japan-Retinal Detachment Registry, organized by the Japanese Retina and Vitreous Society, between February 2016 and March 2017. Data obtained from general ophthalmic examinations performed before and at 1, 3, and 6 months after surgery were analyzed. Results: We included 2013 eyes of 2013 patients (men, 1326 (65.9%); mean age, 55.2 ± 15.2 years) from amongst 3446 registered patients. Preoperative PVR-C was observed in 3.6% of patients. Propensity score matching revealed that a shorter axial length (AL) was a risk factor for preoperative PVR-C (OR (Odds Ratio), 0.81; 95% CI (Confidence Interval), 0.69 to 0.96; p = 0.015), which was a risk factor for surgical failure (OR, 4.22; 95% CI, 1.12 to 15.93; p = 0.034); the association was particularly significant for eyes with an AL < 25.0 mm (p = 0.016), while it was insignificant for eyes with an AL ≥ 25.0 mm. Conclusions: A shorter AL was related to the development of PVR-C before surgical invasion. Our results will help elucidate the fundamental pathogenesis of PVR and caution clinicians to meticulously examine eyes with a shorter AL to detect retinal detachment before PVR development.
Magnetic Molecularly Imprinted Nano-Conjugates for Effective Extraction of Food Components—A Model Study of Tyramine Determination in Craft Beers

In this paper, magnetic molecularly imprinted nano-conjugates were synthesized to serve as selective sorbents in a model study of tyramine determination in craft beer samples. The molecularly imprinted sorbent was characterized in terms of morphology, structure, and composition. The magnetic dispersive solid phase extraction protocol was developed and combined with liquid chromatography coupled with mass spectrometry to determine tyramine. Ten samples of craft beers were analyzed using a validated method, revealing tyramine concentrations in the range between 0.303 and 126.5 mg L−1. Tyramine limits of detection and quantification were 0.033 mg L−1 and 0.075 mg L−1, respectively. Therefore, the fabricated molecularly imprinted magnetic nano-conjugates with a fast magnetic responsivity and desirable adsorption performance could be an effective tool for monitoring tyramine levels in beverages.
Small Extracellular Vesicles and Metastasis—Blame the Messenger

Simple Summary Due to their systemic nature, metastatic lesions are a major problem for curative cancer treatment. According to a common model for metastasis, tumor cells disseminate by local invasion, survival in the blood stream and extravasation into suitable tissue environments. At secondary sites, metastatic cells adapt, proliferate and foster vascularization to satisfy nutrient and oxygen demand. In recent years, tumors were shown to extensively communicate with cells in the local microenvironment and future metastatic sites by secreting small extracellular vesicles (sEVs, exosomes). sEVs deliver bioactive cargos, e.g., proteins, and in particular, several nucleic acid classes to reprogram target cells, which in turn facilitate tumor growth, cell motility, angiogenesis, immune evasion and establishment of pre-metastatic niches. sEV-cargos also act as biomarkers for diagnosis and prognosis. This review discusses how tumor cells utilize sEVs with nucleic acid cargos to progress through metastasis, and how sEVs may be employed for prognosis and treatment. Abstract Cancer is a complex disease, driven by genetic defects and environmental cues. Systemic dissemination of cancer cells by metastasis is generally associated with poor prognosis and is responsible for more than 90% of cancer deaths. Metastasis is thought to follow a sequence of events, starting with loss of epithelial features, detachment of tumor cells, basement membrane breakdown, migration, intravasation and survival in the circulation. At suitable distant niches, tumor cells reattach, extravasate and establish themselves by proliferating and attracting vascularization to fuel metastatic growth. These processes are facilitated by extensive cross-communication of tumor cells with cells in the primary tumor microenvironment (TME) as well as at distant pre-metastatic niches. A vital part of this communication network are small extracellular vesicles (sEVs, exosomes) with a size of 30–150 nm. Tumor-derived sEVs educate recipient cells with bioactive cargos, such as proteins, and in particular, major nucleic acid classes, to drive tumor growth, cell motility, angiogenesis, immune evasion and formation of pre-metastatic niches. Circulating sEVs are also utilized as biomarker platforms for diagnosis and prognosis. This review discusses how tumor cells facilitate progression through the metastatic cascade by employing sEV-based communication and evaluates their role as biomarkers and vehicles for drug delivery.
Extra-framework charge and impurities effect, Grand Canonical Monte Carlo and volumetric measurements of CO2/CH4/N2 uptake on NaX molecular sieve

ABSTRACT In this work, Monte Carlo simulation of CO2, N2, and CH4 adsorption on zeolite 13X is carried out in grand canonical ensemble. FAU framework was used to reproduce the structure of zeolite 13X. Universal force field was used to calculate the interactions between adsorbates and 13X. Metropolis method was used for calculating adsorption isotherm. Volumetric measurements were carried out to confirm the simulation results. The simulation results using Universal force field showed good agreement with experimental results. Highest CO2 uptake for this zeolite was found as 5.67 mol/kg from GCMC. Isosteric heat of adsorption was investigated to find the heat released during adsorption of each gas. The simulation result of isosteric heat of adsorption for CO2, N2, and CH4 was utmost 17.00, 4.37, and 6.14 kcal/mole, respectively. Radial distribution graphs were used to find affinity of constituents of zeolite for CO2. Henry’s constant evaluation was also performed at low pressure to find the selectivity of the structure. Henry’s constant of CO2 in an equimolar mixture of N2 and CH4 was calculated 3.49 and 1.49 mol/kg.kPa, respectively. Finally, simulation results were fitted to Toth and dual-site Langmuir isotherms to find the best fit that belongs to dual-site Langmuir.