Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR-486-5p Targets CD133+ Lung Cancer Stem Cells through the p85/AKT Pathway

Despite improvements in therapies and screening strategies, lung cancer prognosis still remains dismal, especially for metastatic tumors. Cancer stem cells (CSCs) are endowed with properties such as chemoresistance, dissemination, and stem-like features, that make them one of the main causes of the poor survival rate of lung cancer patients. MicroRNAs (miRNAs), small molecules regulating gene expression, have a role in lung cancer development and progression. In particular, miR-486-5p is an onco-suppressor miRNA found to be down-modulated in the tumor tissue of lung cancer patients. In this study, we investigate the role of this miRNA in CD133+ lung CSCs and evaluate the therapeutic efficacy of coated cationic lipid-nanoparticles entrapping the miR-486-5p miRNA mimic (CCL-486) using lung cancer patient-derived xenograft (PDX) models. In vitro, miR-486-5p overexpression impaired the PI3K/Akt pathway and decreased lung cancer cell viability. Moreover, miR-486-5p overexpression induced apoptosis also in CD133+ CSCs, thus affecting the in vivo tumor-initiating properties of these cells. Finally, we demonstrated that in vivo CCL-486 treatment decreased CD133+ percentage and inhibited tumor growth in PDX models. In conclusion, we provided insights on the efficacy of a novel miRNA-based compound to hit CD133+ lung CSCs, setting the basis for new combined therapeutic strategies.
The Associations of Dietary Copper with Cognitive Outcomes: The ARIC Study.

Dietary copper intake may be associated with cognitive decline and dementia. We used data from 10,269 participants of the Atherosclerosis Risks in Communities Study to study the associations of dietary copper intake with 20-year cognitive decline and incident dementia. Dietary copper intake from food and supplements was quantified using food frequency questionnaires. Cognition was assessed using three cognitive tests at study visits; dementia was ascertained at study visits and via surveillance. Multiple imputation by chained equations was applied to account for the missing information of cognitive function during follow-up. Survival analysis with parametric models and mixed-effect models were used to estimate the associations for incident dementia and cognitive decline, respectively. During 20 years of follow-up (1996-1998 to 2016-2017), 1,862 incident cases of dementia occurred. Higher intake of dietary copper from food was associated with higher risk of incident dementia among those with high intake of saturated fat (hazards ratio: 1.49, 95% confidence interval (CI): 1.04, 1.95). Higher intake of dietary copper from food was associated with greater decline in language overall (beta: -0.12, 95% CI: -0.23, -0.02). Therefore, a diet high in copper, particularly when combined with a diet high in saturated fat, may increase the risk of cognitive impairment.
Sharp Lagrange multipliers for set-valued optimization problems

In this paper, we give a comparison between some notions of weak sharp minima introduced in [5,15,43] for set-valued optimization problems. Besides, we establish sharp Lagrange multiplier rules for general constrained set-valued optimization problems involving new scalarization functionals based on the oriented distance. Moreover, we provide sufficient optimality conditions for the considered problems without any convexity assumptions.
An increase in early cancer detection rates at a single cancer center: Experiences from Sun Yat-sen University Cancer Center

Cancer has become a major fatal disease in China. The relatively lower early detection rates for multiple cancer types have been one of the main reasons for a relatively lower cancer curative rate in China compared with the developed countries. To investigate trends in the early cancer detection rate over the past 5 years in a major city of China, 45,260 patients with newly diagnosed cancers of the nasopharynx, lung, thyroid, colorectum, liver, breast, uteral cervix, stomach, esophagus, blood, and kidney from 2016 to 2020 at Sun Yat-sen University Cancer Center were evaluated. The early detection rate (stage I disease) for all cancer types in combination significantly increased from 14.4 to 23.07%. Among the studied cancer types, a significant increase in stage I cancers was proportionally seen in cancers of the lung, thyroid, colorectum, and uterine cervix. While for cancers of the liver and stomach, a significant proportional increment was only observed when combining stage I and stage II diseases. No significant alteration in early cancer detection of the nasopharynx, breast, esophagus, blood, or kidney was observed. Three limitations of this present study include relatively small cohorts of cancer patients, relatively short observation periods, and limited sample representativeness. Further efforts are anticipated to validate our findings with larger patient cohorts from different parts of China and enhance early cancer detection rates by promoting public awareness, applying better health care policies, and improving insurance coverage and medical resources.
Ozone Kinetic Studies Assessment for the PPCPs Abatement: Mixtures Relevance

The increasing consumption of pharmaceutical and personal care products (PPCPs) by humankind has been causing an accumulation of contaminants (commonly referred to as contaminants of emerging concern), in effluents and water resources. Ozonation can be used to improve the removal of these contaminants during water treatment to alleviate this burden. In this work, the degradation of methyl (MP), propylparaben (PP), paracetamol (PCT), sulfamethoxazole (SMX), and carbamazepine (CBZ) by ozonation was assessed both for individual compounds and for mixtures with increasing complexity (two to five compounds). Ozonation was performed at pH3 to gain an insight on the exclusive action of molecular ozone as oxidizing agent. The degradation of contaminants was described as a function of time and transferred ozone dose, and the corresponding pseudo-first order kinetic rate constants (k’) were determined. PPCPs were degraded individually within 1.5 to 10 min. CBZ was the most quickly degraded (k’ = 1.25 min−1) and MP the most resistant to ozone (k’ = 0.25 min−1). When in the mixture, the degradation rate of the contaminants was slower. For parabens, the increase of the number of compounds in the mixture led to an exponential decrease of the k’ values. Moreover, the presence of more PPCPs within the mixture increased energy consumption associated with the treatment, thereby reflecting higher economic costs.
Evaluation of Host Resistance, Hydrated Lime, and Weed Control to Manage Clubroot in Canola

Plasmodiophora brassicae Wor. is a soilborne parasite causing clubroot of canola (Brassica napus L.), a serious disease managed mostly by planting clubroot-resistant (CR) cultivars. Recently, new pathotypes of P. brassicae have emerged that overcome resistance, highlighting the need for a greater understanding of resistance stewardship and an integrated approach to clubroot management. Replicated field experiments were conducted in Edmonton, AB, in 2018 and 2019, to evaluate the effect of lime application and weed management on clubroot severity, crop yield and various growth parameters in clubroot-susceptible (CS) and CR canola cultivars. P. brassicae resting spore densities were also monitored by quantitative PCR for each treatment. When hydrated lime was applied to increase the soil pH from initial values of 5.2–5.5 to 7.2, clubroot severity decreased by 34–36% in the CS canola cultivar, while seed yield increased by 70–98%. The application of hydrated lime also resulted in resting spore densities that were 48–80% lower, relative to untreated controls, in plots where the CS cultivar was grown. Lime application or management of weeds did not significantly affect spore densities in plots with the CR cultivar. The results from the field trial suggest that the application of hydrated lime may be a useful strategy to manage clubroot, when used in combination with genetic resistance to reduce disease pressure.
Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats

One of the major aggressive factors that affect gastric injury is non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin (Indo) showed higher potentiality in gastric injury over conventional NSAIDs. Piceatannol (PIC) is a natural polyphenolic stilbene that possesses potent antioxidant and anti-inflammatory properties. The gastroprotective properties of PIC have been overlooked previously. Hence, we aim to study gastric injury induced by Indo and the protective action manifested by PIC, as well as to elucidate the likely underlying mechanisms of action in a rat model. The rats have been treated with vehicle, Indo alone, combined treatment with Indo, and PIC at (5 mg/kg or 10 mg/kg), respectively. The rats were also treated with Indo and omeprazole. In our study, we found that PIC at both 5 and 10 mg/kg doses was effective by averting the rise in ulcer and lesion indices, acid production, and histological variations persuaded by Indo. Mechanistically, PIC significantly reduced lipid peroxidation product (MDA), increased the GSH content, and enhanced SOD and CAT activity. In addition, PIC exhibits a distinct reduction in the levels of inflammatory parameters (Cox-2, IL-6, TNF-α, and NFκB). Contrastingly, PIC augmented both mucin and PGE2 content. Moreover, PIC fostered angiogenesis by increasing the expression of proangiogenic factors (VEGF, bFGF, and PDGF). Overall, the above results suggest PIC exhibits a potential protective effect against Indo-induced gastric ulcers by the antioxidant, anti-inflammatory, and angiogenic mechanisms.
The Integrated Probiotic Database: a genomic compendium of bifidobacterial health-promoting strains

Background: The World Health Organization defines probiotics as “live microorganisms, which when administered in adequate amounts confer a health benefit on the host”. In this framework, probiotic strains should be regarded as safe for human and animal consumption, i.e., they should possess the GRAS (generally recognized as safe) status, notified by the local authorities. Consistently, strains of selected Bifidobacterium species are extensively used as probiotic agents to prevent and ameliorate a broad spectrum of human and/or animal gastrointestinal disorders. Even though probiotic properties are often genus- or species-associated, strain-level differences in the genetic features conferring individual probiotic properties to commercialized bifidobacterial strains have not been investigated in detail. Methods: In this study, we built a genomic database named Integrated Probiotic DataBase (IPDB), whose first iteration consists of common bifidobacterial strains used in probiotic products for which public genome sequences were available, such as members of B. longum subsp. longum, B. longum subsp. infantis, B. bifidum, B. breve, and B. animalis subsp. lactis taxa. Furthermore, the IPDB was exploited to perform comparative genome analyses focused on genetic factors conferring structural, functional, and chemical features predicted to be involved in microbe-host and microbe-microbe interactions. Results and conclusion: Our analyses revealed strain-level genetic differences, underlining the importance of inspecting the strain-specific and outcome-specific efficacy of probiotics. In this context, IPDB represents a valuable resource for obtaining genetic information of well-established bifidobacterial probiotic strains.
Childhood Attention-Deficit/Hyperactivity Disorder: A Research Review

Attention-deficit hyperactivity disorder (ADHD) belongs to the category of neurodevelopmental disorders. The morbidity among worldwide school-aged children is 5%, and 30% to 50% of it would continue to be influenced by the subsequent syndrome. The importance of exploring ADHD is very obvious and vital: to attract people’s attention to ADHD for better understanding and care for this minor population of ADHD children. Three aspects were explored and elaborated on in this research: etiology, treatment, and impact. In etiology, biological and environmental factors are mentioned. The treatment methods include both pharmacological aspects, which brings up stimulant and non-stimulant medication, and the non-pharmacological aspect, which considers behavioral parenting strategies and cognitive behavioral therapy. As for impact, we focus on how ADHD affects children’s social interaction from the perspective of individuals, family, and society. We hope to provide general information on ADHD in helping children with ADHD better adapt and live in this society.
The UV-B-Induced Transcription Factor HY5 Regulated Anthocyanin Biosynthesis in Zanthoxylum bungeanum

Pericarp color is an important economic characteristic of Zanthoxylum bungeanum. Anthocyanins are the main reason for the pericarp’s red appearance in Z. bungeanum. In this study, through the combined analysis of the metabolome and transcriptome, HY5, whose expression is highly correlated to changes in the anthocyanin content, was screened and identified. Under natural ripening conditions, the Z. bungeanum fruit gradually changed in color from green to red, while bagging resulted in the fruit maintaining its green color. After unbagging, the fruit gradually turned red, and the ZbHY5 expression and anthocyanin content increased. In addition, the leaves changed from green to red after exposure to UV-B radiation, and the ZbHY5 expression and anthocyanin content increased. The transient overexpression of ZbHY5 deepened the redness of the Z. bungeanum leaves and promoted the expression of ZbHY5 and ZbMYB113 as well as anthocyanin accumulation. Bimolecular fluorescence complementation (BIFC) showed that there was an interaction between ZbHY5 and ZbMYB113. These results revealed that under UV-B irradiation, ZbHY5 might regulate the expression levels of the structural genes related to anthocyanin biosynthesis through combination with ZbMYB113, thereby affecting anthocyanin accumulation. This finding provides useful insights for further studies focusing on UV-B-induced anthocyanin accumulation in Z. bungeanum.
Smart Monitoring System for Chronic Kidney Disease Patients based on Fuzzy Logic and IoT

A Chronic Kidney Disease (CKD) monitoring system was proposed for early detection of cardiovascular disease (CVD) and anemia using Fuzzy Logic. To determine the heart rate and blood oxygen saturation, the proposed model was simulated using MATLAB and Simulink to handle ECG and PPG inputs. The Pan-Tompkins method was used to determine the heart rate, while the Takuo Aoyagi algorithm was used to assess blood oxygen saturation levels. The findings show that the ECG recorded using the CKD model has all of the characteristics of a typical ECG wave cycle, but with reduced signal degradation in the 0.8–1.3mV region. The heart rate signal processing yielded findings between 78 and 83 beats per minute is within the range of the supplied heart rate. Takuo Aoyagi's pulse oximeter simulation generated the same findings. For real-time verification, the proposed model was implemented in hardware using ESP8266 32-bit microcontroller with IoT integration via Wireless Fidelity for data storage and monitoring. In comparison with the Fuzzy Logic simulation done on MATLAB and Simulink, the CKD monitoring device has 100% accuracy in patient status detection. The CKD monitoring system has an overall accuracy of 99% in comparison with a commercial fingertip pulse oximeter. Keywords—Anemia; cardiovascular disease (CVD); fuzzy logic; healthcare; internet of things
Stakeholders’ involvement in service delivery at eDumbe Municipality

Using a participatory democracy framework, this study assesses the involvement of stakeholders in service delivery at the eDumbe Municipality. This article argues that the interests of stakeholders have been overlooked by municipal officials of eDumbe. The current local government environment is volatile, and municipalities must adapt to constant environmental changes. The principles of cooperative government are provided by the constitution (1996) to be used as a mechanism that can restore peace and relations between officials and the communities. The complexity of municipalities is also exacerbated by political will that is influential on the state power use (Mohale 2017:53).
Defining integrity: An approach and military application

ABSTRACT Personnel selection research has seen an increasing interest in integrity tests. Although these tests have been found to predict a variety of workplace criteria, a long-standing criticism of integrity tests is their criterion-focussed nature. A construct-oriented approach to integrity test development involves identifying important elements of integrity and developing content to reflect those elements. Drawing upon earlier attempts to define integrity, this paper conceptualizes integrity as a behavior, and elaborates on two definitional elements, nature of standards and their referent. Undertaking a content analysis of the high-level codes of conduct of 13 military nations, this paper illustrates the application of an approach to defining integrity for use in the military context. It includes a discussion on the operationalization of integrity for assessment purposes, highlighting considerations that must be given to all aspects of the assessment development process.
Chondroprotective Effects of 4,5-Dicaffeoylquinic Acid in Osteoarthritis through NF-κB Signaling Inhibition

Osteoarthritis (OA) is characterized by cartilage degradation, inflammation, and pain. The dicaffeoylquinic acid (diCQA) isomer, 4,5-diCQA, exhibits antioxidant activity and various other health-promoting benefits, but its chondroprotective effects have yet to be elucidated. In this study, we aimed to investigate the chondroprotective effects of 4,5-diCQA on OA both in vitro and in vivo. Primary rat chondrocytes were pre-treated with 4,5-diCQA for 1 h before stimulation with interleukin (IL)-1β (5 ng/mL). The accumulation of nitrite, PGE2, and aggrecan was observed using the Griess reagent and ELISA. The protein levels of iNOS, COX-2, MMP-3, MMP-13, ADMATS-4, MAPKs, and the NF-κB p65 subunit were measured by Western blotting. In vivo, the effects of 4,5-diCQA were evaluated for 2 weeks in a destabilization of the medial meniscus (DMM)-surgery-induced OA rat model. 4,5-diCQA significantly inhibited IL-1β-induced expression of nitrite, iNOS, PGE2, COX-2, MMP-3, MMP-13, and ADAMTS-4. 4,5-diCQA also decreased the IL-1β-induced degradation of aggrecan. It also suppressed the IL-1β-induced phosphorylation of MAPKs and translocation of the NF-κB p65 subunit to the nucleus. These findings indicate that 4,5-diCQA inhibits DMM-surgery-induced cartilage destruction and proteoglycan loss in vivo. 4,5-diCQA may be a potential therapeutic agent for the alleviation of OA progression. In this study, diclofenac was set to be administered once every two days, but it showed an effect on OA. These results may be used as basic data to suggest a new dosing method for diclofenac.
Correlation of Genetic Variants and the Incidence, Prevalence and Mortality Rates of Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, representing about 30–35% of cases. Its etiology is complex and not fully understood. ALL is influenced by genetic variants, and their frequencies (Fq) vary in different ethnic groups, which consequently could influence the epidemiology of this cancer worldwide. The aim of this study was to investigate the correlation between the genetic variants and their impacts on incidence (IC), mortality (MT), and prevalence (PV) rates of ALL in different world populations. Methods: Sixty variants were selected from the literature with Genome Wide Association studies (GWAS). Information regarding allele Fq was selected from the 1000 Genomes platform. Epidemiological data were taken from the Global Burden of disease visualisations (GBD) Compare website. Statistical analyses were calculated in RStudio v.3. 5.1 software. Results: Four variants demonstrated significant results in correlations with epidemiological data for ALL. The PAX5 gene variant (rs2297105) had an indirect relationship with PV and IC of ALL, showing that an increased Fq of this variant is related to low rates of both. An increased Fq of rs915172 in EPB4IL2 gene was also correlated with a lower IC of ALL. The rs1048943 of the CYP1A1 gene and the rs3088440 polymorphism of the CDKN2A gene were shown to have a direct proportional relationship with MT rate, showing that an increased Fq of these variants correlates with a worse prognosis worldwide. Conclusion: Our study points out four important variants for understanding the IC, PV, and MT rates for ALL. The ascertainment of these data may help to choose molecular markers to investigate the susceptibility and prognosis of ALL.
No pain, no gain! The uncertainty-to-win effect on customer experience quality through gamified interaction

Offering customers a high-quality experience has become critical for companies. Scholars have therefore emphasized the opportunity to use gamification. However, despite the increasing popularity of such an approach, prior studies report mixed results. This research aims to reconcile these findings by identifying under which conditions gamification leads to a better experience. Drawing on uncertainty-resolution theory, we examine how uncertainty-to-win affects customer experience quality. The results from six studies, combining a field study and experiments, demonstrate the benefits of uncertainty-to-win for customer experience quality. We find that the uncertainty-to-win effect persists even after people are informed of a win/lose decision. Moreover, we highlight that losing the contest stresses the uncertainty-to-win effect, and consequently counter the harmful effect of loss. Conversely, we suggest that reward value mitigates the positive impact of uncertainty-to-win by focusing customers’ attention on a prize instead of on their experience. Our findings move the literature forward by underscoring how uncertainty-to-win is a condition that explains gamification’s ability to deliver a high-quality experience.
The Use of Machine-Learning Techniques in Material Constitutive Modelling for Metal Forming Processes

Accurate numerical simulations require constitutive models capable of providing precise material data. Several calibration methodologies have been developed to improve the accuracy of constitutive models. Nevertheless, a model’s performance is always constrained by its mathematical formulation. Machine learning (ML) techniques, such as artificial neural networks (ANNs), have the potential to overcome these limitations. Nevertheless, the use of ML for material constitutive modelling is very recent and not fully explored. Difficulties related to data requirements and training are still open problems. This work explores and discusses the use of ML techniques regarding the accuracy of material constitutive models in metal plasticity, particularly contributing (i) a parameter identification inverse methodology, (ii) a constitutive model corrector, (iii) a data-driven constitutive model using empirical known concepts and (iv) a general implicit constitutive model using a data-driven learning approach. These approaches are discussed, and examples are given in the framework of non-linear elastoplasticity. To conveniently train these ML approaches, a large amount of data concerning material behaviour must be used. Therefore, non-homogeneous strain field and complex strain path tests measured with digital image correlation (DIC) techniques must be used for that purpose.