Miracle-dz/UniFAR-FTUs huggingface dataset:
(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg−1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2–6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.
MCPH1 Lack of Function Enhances Mitotic Cell Sensitivity Caused by Catalytic Inhibitors of Topo II

The capacity of Topoisomerase II (Topo II) to remove DNA catenations that arise after replication is essential to ensure faithful chromosome segregation. Topo II activity is monitored during G2 by a specific checkpoint pathway that delays entry into mitosis until the chromosomes are properly decatenated. Recently, we demonstrated that the mitotic defects that are characteristic of cells depleted of MCPH1 function, a protein mutated in primary microcephaly, are not a consequence of a weakened G2 decatenation checkpoint response. However, the mitotic defects could be accounted for by a minor defect in the activity of Topo II during G2/M. To test this hypothesis, we have tracked at live single cell resolution the dynamics of mitosis in MCPH1 depleted HeLa cells upon catalytic inhibition of Topo II. Our analyses demonstrate that neither chromosome alignment nor segregation are more susceptible to minor perturbation in decatenation in MCPH1 deficient cells, as compared with control cells. Interestingly, MCPH1 depleted cells were more prone to mitotic cell death when decatenation was perturbed. Furthermore, when the G2 arrest that was induced by catalytic inhibition of Topo II was abrogated by Chk1 inhibition, the incidence of mitotic cell death was also increased. Taken together, our data suggest that the MCPH1 lack of function increases mitotic cell hypersensitivity to the catalytic inhibition of Topo II.
Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway.

PURPOSE The current study aimed at investigating the anticancer effects of plant-based flavone Baicalein against the thyroid cancer. METHODS Cell viability was assessed using MTT assay. Flow cytometric-based estimation of cell cycle analysis was done for determining the cancer cell phase distribution. DAPI staining method followed by fluorescent microscope examination was used for inferring the cancer cell apoptosis. Transmission electron microscopy (TEM) was used for detection of autophagosomes. Western blotting was done for protein concentration estimation. RESULTS Baicalein induced dose-dependent decline in proliferation of MDA-T68 thyroid cancer cells, while the reduction of cell proliferation was surprisingly lower for normal thyrocytes. IC50 of 10μM was estimated against cancer cells. Baicalein induced cell apoptosis in a concentration-dependent manner. Induction of apoptosis was attributed to increase in apoptotic protein concentration and signal was mediated through change Bax/Bcl-2 ratio. The autophagic cell death occurred in cancer cells when treated with Baicalein. The mechanism of cell death was inferred as modulation of NF-kB signaling pathway. Baicalein was also seen to induce mitotic cell cycle arrest in thyroid cancer cells by reducing the concentration of Cyclin B1 mitotic protein. CONCLUSION The results of current study suggest Baicalein as an important anticancer agent against thyroid cancer. Future research to further investigate and enhance the effects of Baicalein against thyroid cancer is needed.
Prophylactic human papillomavirus vaccination to prevent recurrence of cervical intraepithelial neoplasia: a meta-analysis

Objective The aim of this systematic review and meta-analysis was to review evidence supporting the use of prophylactic human papillomavirus (HPV) vaccines to influence the risk of recurrence of cervical intraepithelial neoplasia after surgical treatment. Methods A systematic literature search was performed for publications reporting risk of recurrence of cervical intraepithelial neoplasia after surgical treatment in patients receiving HPV vaccination (either in the prophylactic or adjuvant setting). Comprehensive searches of six electronic databases (MEDLINE, Embase, Web of Science, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and references of identified studies) from their inceptions were performed (English language only), and hand search reference lists were performed. Two independent reviewers applied inclusion and exclusion criteria to select manuscripts, with differences discussed and agreed by consensus. The literature search was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). Results A total of 5744 citations were reviewed; 5 studies comprising 2912 patients were selected for the analysis. There were 1338 patients in the vaccinated group and 1574 in the placebo or unvaccinated group. The incidence of histologically confirmed cervical intraepithelial neoplasia 2+ was reduced in the vaccinated compared to the unvaccinated group (OR 0.34, 95% CI 0.21–0.54, p=< 0.00001). The number needed to treat to prevent one recurrence was 27. Both pre-treatment vaccination (OR 0.40, 95% CI 0.21–0.78, p=0.007, number needed to treat – 37) and adjuvant vaccination (OR 0.28, 95% CI 0.14–0.56, p=0.0003, number needed to treat – 30) reduced recurrence rates. Conclusion Prophylactic or adjuvant HPV vaccination reduces the risk of recurrent cervical intraepithelial neoplasia 2+. These data support further investigation of its role as an adjuvant to surgical treatment.
Mitochondrial morphology and function: two for the price of one!

Mitochondrial shape and function are known to be linked; therefore, there is a need to combine three‐dimensional EM structural analysis with functional analysis. Cytochrome c oxidase labelling is one approach to examine mitochondrial function at the EM level. However, previous efforts to apply this method have had several issues including inconsistent results, disruption to mitochondrial ultrastructure, and a lack of optimisation for volume EM methods. We have used short fixation and microwave processing to address these issues. We show that our method gives consistent cytochrome c oxidase labelling and improves labelling penetration across tissue volume. We also quantify mitochondrial morphology metrics, including in volume EM, to show that ultrastructure is unaltered by the processing. This work represents a technical advance that allows the correlation of mitochondrial function and morphology with greater resolution and volume than has previously been feasible.
Inhibition of cancer cell growth in cisplatin-resistant human oral cancer cells by withaferin-A is mediated via both apoptosis and autophagic cell death, endogenous ROS production, G2/M phase cell cycle arrest and by targeting MAPK/RAS/RAF signalling pathway.

PURPOSE Oral cancer is one of the common oral cavity and pharynx cancers and its treatment is limited by early metastasis, late diagnosis and emergence of drug resistance. Herein we investigated the anticancer effects of Withaferin-A against the cisplatin-resistant SCC-4 human oral cancer cells. METHODS The proliferation rate of the human oral cancer cells was evaluated by CCK-8 assay. Apoptotic cell death was studied by acridine orange (AO) / ethidium bromide (EB) staining as well as by flow cytometry using annexin V/propidium iodide (PI) staining. Cell cycle analysis was performed by flow cytometry. Reactive oxygen species (ROS) examination was carried out by flow cytometry. Protein expressions were determined by immunoblotting. RESULTS The results of the MTT assay showed that Withaferin-A caused decrease in the proliferation of SCC-4 cells and exhibited an IC50 of 14 µM. The anticancer effects of Withaferin-A were mainly due to the induction of apoptosis which was linked with upsurge of Bax and depletion of BCl-2. Annexin V/PI assay showed that the apoptotic cells were 0.75, 5.8, 12.4 and 22.66% at 0,7,14 and 28 µM concentrations of Withaferin-A. Withaferin-A also caused increase in the ROS and decrease in the MMP levels of the SCC-4 cells. Western blot analysis showed that the expression of LC3B II increased while of p62 decreased remarkably upon treatment with Withaferin-A, suggestive of autophagic cell death. Cell cycle analysis by flow cytometry showed that Withaferin-A caused increase in the G2/M phase cells triggering arrest of cancer cells at the G2/M checkpoint of the cell cycle. Finally, western blot analysis showed that Withaferin-A blocked the MAPK/RAS/RAF signalling pathway in the SCC-4 cells. CONCLUSIONS These results suggest that Withaferin-A may prove a potent lead molecule in oral cancer treatment and warrants further investigations.
Endoscopic adenoidectomy: a systematic analysis of outcomes and complications in 1006 patients

SUMMARY Adenoid hypertrophy (AH) is an extremely common condition in the paediatric population, relating to different pathological scenarios. Failure in responding to medical therapy often leads to adenoidectomy. While traditional adenoidectomy is indeed a relatively “blind” procedure, endoscopic procedures allow more radical resections, bleeding monitoring and complete Eustachian tube sparing, making adenoidectomy a safer, more manageable and functional procedure. Though the literature widely describes endoscopic adenoidectomy, only small case series are available and the procedure itself has never really taken hold in routine otolaryngology practice. The aim of this article is to report data on endoscopic adenoidectomy in a large single centre patient population. We retrospectively evaluated the medical records of 1006 children who underwent endoscopic adenoidectomy with or without tonsillectomy (respectively 493 and 513 patients). Data on surgical time, blood loss, hospital stay, short and long-term complications, recurrences and post-operative pain were collected. Our analysis showed that the endoscopic approach requires a longer surgical time, but it is associated with less intraoperative blood loss, a lower complication rate and less treatment failures compared to large contemporary case series of either traditional or power-assisted approaches. The overall better outcomes are more noticeable when comparing our data with classic technique case series than with power-assisted case series. Endoscopic adenoidectomy should therefore be regarded as a valid technique, which, in expert hands, lowers the rates of complications and recurrences at the expense of a slightly increased surgical time.
Software Development Effort Estimation from Unstructured Software Project Description by Sequence Models

SUMMARY Most existing methods of e ﬀ ort estimations in software development are manual, labor-intensive and subjective, resulting in over-estimation with bidding fail, and underestimation with money loss. This paper investigates e ﬀ ectiveness of sequence models on estimating development e ﬀ ort, in the form of man-months, from software project data. Four architectures; (1) Average word-vector with Multi-layer Perceptron (MLP), (2) Average word-vector with Support Vector Regression (SVR), (3) Gated Recurrent Unit (GRU) sequence model, and (4) Long short-term memory (LSTM) sequence model are compared in terms of man-months di ﬀ erence. The approach is evaluated using two datasets; ISEM (1,573 English software project descriptions) and ISBSG (9,100 software projects data), where the former is a raw text and the latter is a structured data table explained the characteristic of a software project. The LSTM sequence model achieves the lowest and the second lowest mean absolute errors, which are 0.705 and 14.077 man-months for ISEM and ISBSG datasets respectively. The MLP model achieves the lowest mean absolute errors which is 14.069 for ISBSG datasets. key words: software e ﬀ ort estimation, regression, deep learning, sequence model,
Awareness on childhood obesity among mothers attending pediatrics outpatient department at tertiary care teaching hospital

Background: Childhood obesity is emerging as a global issue that needs more focus nationally and internationally. Increased calorie intake along with decreased physical activity among children is on the rise that has been responsible for unhealthy weight gain. Health education is essential to tackle decreased awareness among mothers regarding childhood obesity. Objectives: (1) The objectives of the study were to know whether mothers are aware about childhood obesity and how it affects their child’s health. (2) To create an awareness about beneficial effects of breastfeeding in prevention of obesity. Materials and Methods: A descriptive cross-sectional study was conducted among mothers attending Paediatric Outpatient Department at Chennai Medical College Hospital and Research Centre, Trichy, from October to November 2017. A total of 200 mothers were studied using pre-structured and pre-designed questionnaire. The data were collected, and statistical analysis was done. Results: Of 200, only 5.6% of study participants had good knowledge, 56.9% poorknowledge, and 37.5% had no knowledge about it. Conclusion: The present study highlights that awareness camps about childhood obesity and overweight must be included in routine health care visits for preventing the current increasing trends of non-communicable diseases.
Altered gender-related homocysteine metabolism and lipid panel in healthy heavy smokers: a possible role for nutraceutical supplementation

In recent years, clinical and epidemiological studies have suggested that increased concentrations of total plasma homocysteine (tHcy) could be an additional independent risk factor for cardiovascular disease [1]. It has been established that a very high tHcy concentration due to inborn metabolic errors causing enzyme alterations in homocysteine metabolism can lead to serious thrombotic events at a young age [2]. Mild to moderate hyperho-
Attribution of the Australian bushfire risk to anthropogenic climate change

Abstract. Disastrous bushfires during the last months of 2019 and January 2020 affected Australia, raising the question to what extent the risk of these fires was exacerbated by anthropogenic climate change. To answer the question for southeastern Australia, where fires were particularly severe, affecting people and ecosystems, we use a physically based index of fire weather, the Fire Weather Index; long-term observations of heat and drought; and 11 large ensembles of state-of-the-art climate models. We find large trends in the Fire Weather Index in the fifth-generation European Centre for Medium-Range Weather Forecasts (ECMWF) Atmospheric Reanalysis (ERA5) since 1979 and a smaller but significant increase by at least 30 % in the models. Therefore, we find that climate change has induced a higher weather-induced risk of such an extreme fire season. This trend is mainly driven by the increase of temperature extremes. In agreement with previous analyses we find that heat extremes have become more likely by at least a factor of 2 due to the long-term warming trend. However, current climate models overestimate variability and tend to underestimate the long-term trend in these extremes, so the true change in the likelihood of extreme heat could be larger, suggesting that the attribution of the increased fire weather risk is a conservative estimate. We do not find an attributable trend in either extreme annual drought or the driest month of the fire season, September–February. The observations, however, show a weak drying trend in the annual mean. For the 2019/20 season more than half of the July–December drought was driven by record excursions of the Indian Ocean Dipole and Southern Annular Mode, factors which are included in the analysis here. The study reveals the complexity of the 2019/20 bushfire event, with some but not all drivers showing an imprint of anthropogenic climate change. Finally, the study concludes with a qualitative review of various vulnerability and exposure factors that each play a role, along with the hazard in increasing or decreasing the overall impact of the bushfires.
Effect of dietary oil seeds on n-3 fatty acid enrichment, performance parameters and humoral immune response of broiler chickens

A 42-day study was conducted to evaluate the influence of full-fat flaxseed (FS) and canola seed (CS) on broiler performance, fatty acid (FA) profile of meat, serum lipid content and antibody response to sheep red blood cells antigen (SRBC). A total of 324 one-day-old chicks were attributed to 6 experimental groups. C: control (soybean-corn); CS1:7.5% CS; CS2:15% CS; CS-FS:10% FS + 10% CS; FS1:7.5% FS; FS2:15% FS. The diets containing FS and CS had a significant negative effect on performance parameters (P<0.01), however, feed consumption was not significantly (P>0.05) different among treatments. Inclusion of FS and CS significantly increased (P<0.01) the concentration of omega-3 FA and decreased the content of the arachidonic acid and n-6:n-3 polyunsaturated FA ratio. The serum lipid content and antibody titre against SRBC were not affected by dietary oil seeds (P>0.05).
EU Financing and Innovation in Poland

Since the collapse of communism, Poland has distinguished itself as one of the best performing economies in the European Union. However, the recent deceleration in growth has raised concerns about a “middle income trap”. Poland ranks among the lowest in the European Union on various measures of innovation, and its innovation system is relatively weak. In this context, the injection of EU funds focused on novel product R&D by private firms is a valuable opportunity. The main fear is that this EU-funded “innovation tsunami” may have negative side effects as well. Accordingly, we offer some policy recommendations under the constraints of an already agreed upon EU programme.
The role of toll like receptor 9 in maintaining gut homeostasis

Toll-Like Receptor 9 (TLR9) is a unique pattern recognition receptor due to its ability to induce either pro- or anti-inflammatory cascades. However, much remains to be elucidated regarding this receptor, such as its localization in different cell and tissue types, the potential epitopes that induce signaling, and how activation of the receptor may result in diverging pathways. Despite these unknowns, the integral role of TLR9 in maintaining gut homeostasis remains clear. In addition to maintaining homeostasis, TLR9 may also have significant potential in treating gut-associated inflammatory diseases such as ulcerative colitis, Crohn’s and inflammatory bowel disease via its anti-inflammatory effects. This review will outline some of the key remaining questions regarding the role TLR9 in the gut and highlight its potential utility as a therapeutic target for gastrointestinal disease.
Identification of Manning’s Coefficient Using HEC-RAS Model: Upstream Al-Amarah Barrage

In understanding the hydraulic characteristics of river system flow, the hydraulic simulation models are essential tools. This study submits the results of the proposition of a hydraulic model in order to determine the roughness coefficient (Manning’s coefficient n) of the Tigris River along 3.5 km within the Maysan Governorate, south of Iraq. HEC-RAS software was the simulation tool used in this study. The HEC-RAS model was adopted, calibrated, and validated in adopting two sets of observed water levels. Graphical and statistical approaches were used for model calibration and verification. Results from this investigation showed that a value of Manning’s coefficient of 0.025 gave an acceptable agreement between observed and simulated values of water levels.
Knee Joint Biomechanics in Physiological Conditions and How Pathologies Can Affect It: A Systematic Review

The knee joint, as the main lower limb motor joint, is the most vulnerable and susceptible joint. The knee injuries considerably impact the normal living ability and mental health of patients. Understanding the biomechanics of a normal and diseased knee joint is in urgent need for designing knee assistive devices and optimizing a rehabilitation exercise program. In this paper, we systematically searched electronic databases (from 2000 to November 2019) including ScienceDirect, Web of Science, PubMed, Google Scholar, and IEEE/IET Electronic Library for potentially relevant articles. After duplicates were removed and inclusion criteria applied to the titles, abstracts, and full text, 138 articles remained for review. The selected articles were divided into two groups to be analyzed. Firstly, the real movement of a normal knee joint and the normal knee biomechanics of four kinds of daily motions in the sagittal and coronal planes, which include normal walking, running, stair climbing, and sit-to-stand, were discussed and analyzed. Secondly, an overview of the current knowledge on the movement biomechanical effects of common knee musculoskeletal disorders and knee neurological disorders were provided. Finally, a discussion of the existing problems in the current studies and some recommendation for future research were presented. In general, this review reveals that there is no clear assessment about the biomechanics of normal and diseased knee joints at the current state of the art. The biomechanics properties could be significantly affected by knee musculoskeletal or neurological disorders. Deeper understanding of the biomechanics of the normal and diseased knee joint will still be an urgent need in the future.