Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting Adipokines in Obesity-Related Tumors

Obesity, a global epidemic, is an independent risk factor for the occurrence and development of a variety of tumorigenesis, such as breast cancer, pancreatic cancer, ovarian cancer and colorectal cancer. Adipocytes are important endocrine cells in the tumor microenvironment of obesity-related tumors, which can secrete a variety of adipokines (such as leptin, adiponectin, estrogen, resistin, MIF and MCP-1, etc.), among which leptin, adiponectin and estrogen are the most in-depth and valuable ones. These adipokines are closely related to tumorigenesis and the progression of tumors. In recent years, more and more studies have shown that under chronic inflammatory conditions such as obesity, adipocytes secrete more adipokines to promote the tumorigenesis and development of tumors. However, it is worth noting that although adiponectin is also secreted by adipocytes, it has an anti-tumor effect, and can cross-talk with other adipokines (such as leptin and estrogen) and insulin to play an anti-tumor effect together. In addition, obesity is the main cause of insulin resistance, which can lead to the increase of the expression levels of insulin and insulin-like growth factor (IGF). As important regulators of blood glucose and lipid metabolism, insulin and IGF also play an important role in the progress of obesity related tumors. In view of the important role of adipokines secreted by adipocytes and insulin/IGF in tumors, this article not only elaborates leptin, adiponectin and estrogen secreted by adipocytes and their mechanism of action in the development of obesity- related tumors, but also introduces the relationship between insulin/IGF, a regulator of lipid metabolism, and obesity related tumors. At the same time, it briefly describes the cancer-promoting mechanism of resistin, MIF and MCP-1 in obesity-related tumors, and finally summarizes the specific treatment opinions and measures for various adipokines and insulin/insulin-like growth factors in recent years.
Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile

Background Clostridioides difficile (C. difficile) is one of the primary pathogens responsible for infectious diarrhea. Antibiotic treatment failure, occurring in about 30% of patients, and elevated rates of antibiotic resistance pose a major challenge for therapy. Reinfection often occurs by isolates that produce biofilm, a protective barrier impermeable to antibiotics. We explored the association between antibiotic resistance (in planktonic form) and biofilm-production in 123 C. difficile clinical isolates. Results Overall, 66 (53.6%) out of 123 isolates produced a biofilm, with most of them being either a strong (44%) or moderate (34.8%) biofilm producers. When compared to susceptible isolates, a statistically higher percentage of isolates with reduced susceptibility to metronidazole or vancomycin were biofilm producers (p < 0.0001, for both antibiotics). Biofilm production intensity was higher among tolerant isolates; 53.1% of the metronidazole-susceptible isolates were not able to produce biofilms, and only 12.5% were strong biofilm-producers. In contrast, 63% of the isolates with reduced susceptibility had a strong biofilm-production capability, while 22.2% were non-producers. Among the vancomycin-susceptible isolates, 51% were unable to produce biofilms, while all the isolates with reduced vancomycin susceptibility were biofilm-producers. Additionally, strong biofilm production capacity was more common among the isolates with reduced vancomycin susceptibility, compared to susceptible isolates (72.7% vs. 18.8%, respectively). The distribution of biofilm capacity groups was statistically different between different Sequence-types (ST) strains (p =0.001). For example, while most of ST2 (66.7%), ST13 (60%), ST42 (80%) isolates were non-producers, most (75%) ST6 isolates were moderate producers and most of ST104 (57.1%) were strong producers. Conclusions Our results suggest an association between reduced antibiotic susceptibility and biofilm production capacity. This finding reinforces the importance of antibiotic susceptibility testing, mainly in recurrence infections that may be induced by a strain that is both antibiotic tolerant and biofilm producer. Better adjustment of treatment in such cases may reduce recurrences rates and complications. The link of biofilm production and ST should be further validated; if ST can indicate on isolate virulence, then in the future, when strain typing methods will be more available to laboratories, ST determination may aid in indecision between supportive vs. aggressive treatment.
Microglia-Specific Expression of HEXA and HEXB Leads to Poor Prognosis in Glioblastoma Patients

Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. β-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, HEXA and HEXB, are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD). However, the expression pattern and function of HEXA and HEXB in GBM remains unclear. Here, we found that both the mRNA and protein expression levels of HEXA and HEXB were significantly upregulated in GBM patient samples. The results from single-cell RNA-sequencing (scRNA-seq) database and double immunostaining showed that HEXA and HEXB were specifically expressed in microglia in GBM patient samples. Furthermore, our in vitro experiments revealed that conditioned media from HEXA and HEXB knockdown-microglia cells could inhibit the proliferation and migration of GBM cells. Finally, according to survival analysis based on online database, higher expression of HEXA and HEXB was associated with poor prognosis in GBM patients. In conclusion, these results suggest that microglial HEXA and HEXB play fundamental role in GBM progression, and they will be potential biomarkers for GBM.
ER Stress and Micronuclei Cluster: Stress Response Contributes to Genome Chaos in Cancer

Micronuclei is a cytogenetic term describing small nuclei composed of one to a few chromosomes or chromosomal fragments, which often result from abnormal cell divisions (Fenech et al., 2016). Micronuclei were discovered by Henry Howell and JustinMarie Jolly in erythrocytes over a century ago (Sears and Udden, 2012). Initially, Howell-Jolly bodies were used to describe the visible DNA fragments following the expulsion of the nucleus. Later on, the term “micronuclei” was adapted to describe all smaller fragments of the nucleus (1/5−1/20 the size of a normal nucleus) (Evans et al., 1959; Schmid, 1975). Micronuclei were initially correlated with conditions such as vitamin B12 and folate deficiency (Dawson and Bury, 1961). Soon thereafter, they were linked to many other genotoxic factors such as chemical exposure and radiation (Fenech et al., 2011). The presence of micronuclei is usually considered as an indicator of DNA damage and defects in mitosis. Several different assays have been developed for the use of micronuclei. The cytokinesis-block, peripheral lymphocytic, and buccal MN assays have all been developed for use in mammalian cells in vivo (Sommer et al., 2020). Particularly, the development of the peripheral lymphocyticMN assay pioneered the use of micronuclei as a biomarker in mammalian cells with higher efficiency, along with a more rigorous definition for scoring (<1/3 of a nucleus, similar staining, no overlap, within 3–4 nuclear diameters from the main nucleus) (Countryman and Heddle, 1976). Recently, enthusiasm for micronuclei studies has reemerged (Xie et al., 2016; Guo et al., 2019, 2020a,b; Fenech, 2020; Lepage et al., 2020; Mirzayans and Murray, 2020). First, the linkage to chromosomal instability, cancer, and other aging-related diseases has made micronuclei a potential potent biomarker (Aranda et al., 2018). Secondly, micronuclei, among many other previously ignored chromosomal abnormalities (most of which belong to the non-clonal chromosome aberrations or NCCAs), are key contributing factors for cancer by re-organizing the karyotype coding (Iourov et al., 2010, 2020; Heng et al., 2013; Ye et al., 2019a). Thirdly, micronuclei involve the activation of the immune system, further broadening the utility of micronuclei (Bartsch et al., 2017; Mackenzie et al., 2017; Kirsch-Volders et al., 2020). Finally, micronuclei are linked to stress response-mediated genome chaos, a driving force for cancer evolution (Heng, 2019; Ye et al., 2019b, 2021; Shoshani et al., 2020).
A Study on the Influencing Factors of Continued Intention to Use MOOCs: UTAUT Model and CCC Moderating Effect

Massive Open Online Courses (MOOCs) is the product of “internet + education,” which offer the open educational resources to global students. This study analyzed the factors influencing the continued intention to use the MOOCs by students. To achieve research objectives, this study integrated the unified theory of acceptance and use of technology (UTAUT) and connected classroom climate (CCC). In this study, 312 valid samples were used to verify the hypothesis proposed with the help of structural equation modeling and PROCESS. The results showed that the factors of UTAUT model (performance expectancy, effort expectancy, social influence, and facilitating conditions) had significant positive effects on continued intention to use MOOCs. More importantly, there was a significant moderating effect of CCC between UTAUT and the continued intention to use MOOCs. Based on this research the findings, implications and limitations are discussed.
Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

Background: Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD). Objectives: (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework. Data Sources: We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020. Original research articles must report a measure of ACD and included individuals with AD dementia, or prodromal AD (or MCI), or being at risk for AD. Data Synthesis: All studies covering preclinical, prodromal, and AD dementia were systematically reviewed. We intended to perform a meta-analysis of empirical studies on preclinical AD or prodromal AD (or MCI), to compare ACD between clinical groups. Due to the paucity of literature on preclinical AD, meta-analysis was only possible for prodromal AD (or MCI) studies. Results: We systematically reviewed 283 articles, and conducted a meta-analysis of 18 articles on prodromal AD (or MCI), showing that ACD was not significantly different between patients with amnestic and non-amnestic MCI (SMD = 0.09, p = 0.574); ACD was significantly poorer in amnestic MCI (SMD = −0.56, p = 0.001) and mild AD (SMD = −1.39, p < 0.001) than in controls; ACD was also significantly poorer in mild AD than in amnestic MCI (SMD = −0.75, p < 0.001), as well as poorer than in non-amnestic MCI (SMD = −1.00, p < 0.001). We also discuss key findings on ACD in AD, such as its neural and cognitive correlates. Conclusions and Implications: We propose that patients may be complaining of their initial subtle cognitive changes, but ACD would soon start to decrease. The individual would show mild anosognosia in the MCI stage, and severe anosognosia in dementia. The evaluation of ACD (comparing self-report to cognitive scores or to informant-report) could be useful to guide the clinician toward a timely diagnosis, and in trials targeting early-stage AD.
Time-Specific Pattern of Iron Deposition in Different Regions in Parkinson's Disease Measured by Quantitative Susceptibility Mapping

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.
Effects of Chitosan and Chitosan Nanoparticles on Water Quality, Growth performance, Survival Rate and Meat Quality of the African Catfish, Clarias Gariepinus

The culture of African catfish (Clarias gariepinus) is hamstrung by high feed cost, and efforts to reduce it have been geared toward exploiting fishmeal alternatives which are hitherto competed for by both human and livestock. There is a growing need to search for waste products which can save this situation. A 91-day feeding trial was conducted in nine tarpaulin tanks with twenty C. gariepinus fingerlings each of average weight 2.79±0.05 g to check the effect of chitosan and its nanoparticles on growth performance and feed utilization. The basal diet (BD) which served as control was formulated to contain 40% crude protein. Two test diets were formulated to contain BD replaced with 5g kg-1 diet of chitosan (BD+CH) and chitosan nanoparticles (BD+CHN) respectively. These were replicated thrice. Chitosan supplementation was found to significantly (P<0.05) improved daily weight gain, survival and meat quality P<0.05) of C. gariepinus fingerlings while chitosan nanoparticle supplementation significantly improved water quality, daily weight gain, feed utilization, survival as well as body composition. Chitosan nanoparticles from shells of arthropods and shellfish which lay waste globally has the potentials to revolutionize aquaculture. Fish nutritionists as well as farm managers should key into this platform technology.
Effect of shocked nitrobenzene concentrations on the operational performance of anaerobic sequential batch reactor

Two lab‐scale anaerobic sequence batch reactors (ASBRs), respectively fed with 5 mg L−1 (R1) and 200 mg L−1 (R2) of sulfate were set up in this study. A mixture of the volatile fatty acids (VFAs) containing acetate and propionate was provided as electron donors. The effects of the influent nitrobenzene (NB) concentrations and the external electron acceptor of sulfate on the operational performance of ASBRs were investigated. The results indicated that NB reduction, sulfate reduction and propionate degradation were inhibited or further terminated in response to a shocked influent NB concentration of 50 mg L−1, i.e., 32 g m−3 day−1. However, these biological activities in ASBRs could be reversibly resumed so long as the influent NB regained below 30 mg L−1. The insufficient propionate was the main electron donor for the simultaneous reductions of NB and sulfate. Sulfate can energetically compete with NB for propionate as a co‐substrate, resulting in the better performance of reactor R1 than that of R2. In engineering applications, the influent loading rates of pollutants should be safely declined below toxic thresholds to avoid the failure of system operation. © 2017 American Institute of Chemical Engineers Environ Prog, 37: 712–718, 2018
Resorcinarene-Embedded Stable Silver Nanoparticles: A Fluorescent Nanoprobe for Pb(II) in Water

Divya Mishra, Anita Kongor, Manthan Panchal, Krunal Modi, Vinod Jain 1, 2, 3, 5 Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad-380009, Gujarat, India J. Heyrovsky Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Dolejškova, 2155/3, 182 23 Prague 8, Czech Republic Abstract: Calix[4] resorcinarene tetrahydrazide capped silver nanoparticles (CRTH-AgNps) were synthesized using a simple chemical reduction method. The silver nanoparticles (AgNps) obtained were used without further modification for the detection of lead and were characterized using surface plasmon resonance (SPR), transmission electron microscopy (TEM) and energy dispersive x-ray analysis (EDX). The stability of the CRTH-AgNps was examined at different pH values and temperatures. The interaction of the CRTH-AgNps with different metal ions was investigated using UV-visible and fluorescence spectroscopy. Their response was found to be highly selective for Pb(II), as the absorption and emission spectra were found to be uninterrupted by the presence of various metal ions, such as Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II). The emission spectra showed that CRTH-AgNps are highly selective and sensitive for Pb(II) by means of fluorescence quenching. The minimum detection limit was found in the range of 1 nM to 0.980 μM. The plausible mechanism is discussed where the carbonyl oxygen and amide nitrogen atoms of CRTH not only participate in the binding with Pb(II) but also behave as a PET acceptor. The synthesized nano-probe was successfully used for the detection of Pb(II) in industrial waste-water samples.
TGF-β1-induced Chloride Channel Activity and Migration of Human Eosinophils

Asthma is a chronic disease of the airways characterized by airway hyperresponsiveness, airway inflammation, and airway remodeling. Eosinophils migrate to the airways and play a significant role in the pathogenesis of asthma, particularly through their release of mediators and cytokines. Transforming growth factor (TGF)-β also induces asthmatic features in the lungs, especially airway remodeling. Eosinophils and TGF-β are closely linked to each other in the induction of airway remodeling. TGF-β activity also affects chloride channel activity, which can regulate mediator release and cell migration. Therefore, the role that TGF-β1 stimulation of eosinophils has on chloride channel activity and migration of eosinophils and the underlying mechanisms involved in this process were examined. Human blood eosinophils were stimulated with TGF-β1, the tyrosine kinase inhibitor genistein, the protein kinase C (PKC)-δ/ε inhibitor rottlerin, the general PKC inhibitor staurosporine, and the chloride channel inhibitors 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). Protein expression of the chloride channel (CLC) family of chloride channels, PKC isozymes, and Smad transcription factors was determined using western blot, and mRNA expression of CLC was examined using RT-PCR. Chloride channel activity was measured by patch clamping, and eosinophil chemotaxis was assessed using a Boyden microchemotaxis chamber. Flow cytometry was used to determine shape change. The results showed that TGF-β1 stimulation increased protein expression of ClC-3. There was also more CLC-3 protein expression in asthmatic eosinophils than normal eosinophils. TGF-β1 increased protein expression of PKC-β1, PKC-δ, and phospho-Smad3. TGF-β1 increased the chloride channel activity of the eosinophils, which was blocked by
Medical exercise and physiotherapy frequency and compliance as predictors for a recurrence of chronic nonspecific low back pain

Purpose A considerable part of nonspecific low back pain patients suffer from a recurrence of symptoms after therapy cessation. The aim of this study was to evaluate the predictive value of active and passive treatments and treatment modalities on a recurrence of back pain after cessation of medically prescribed therapy. Methods Patients with unspecific low back pain from a health- and therapy-center were included. Treatments and treatment modalities as therapy measures were monitored and categorized as active or passive measures. During the year after therapy cessation, patients were monitored to retrieve information about recurrence of symptoms. Patients were dichotomized (recurrence versus no recurrence). An ROC-Analysis was used to determine optimal cut-offs for relevant treatment characteristics’ impact on recurrence risk. The relative risk for a recurrence was calculated based on Chi 2 -test. Results Data from 96 patients (56f, 49±11 years) were analysed. A total of 34 patients had recurring back pain. The frequency of active treatment differed significantly between groups with or without recurrence. A therapy frequency of 1.45 active treatments/week was a sensitive cut-off (sensitivity: 0.73) to discriminate the recurrence groups. Participants with a therapy frequency of less than 1.45 treatments per week showed an 82% increased relative recurrence risk (RR: 1.824 (95%-CI: 1.077-3.087)). Conclusions The results empathize the importance of active treatments (i.e. exercise) in the therapy and (secondary) prevention of unspecific low back pain. Less than 1.45 active treatment sessions/week increases the 1-year-risk of a recurrence by 82%.
Process analytical technology for cheese manufacture

Recent research on the development and application of process analytical technology (PAT) for cheese manufacture is reviewed in this article. PAT is a framework for innovative process manufacturing and quality assurance, which has been widely investigated for dairy processing applications, where particular processing challenges arise due to the variations in the physiochemical properties of milk. Cheese manufacturers are increasingly considering the adoption of a PAT approach to facilitate manufacture of cheese with enhanced product quality, safety and process efficiency. However, to date adoption of PAT in the dairy industry has been limited due to challenges associated with development and validation of calibration models, instrument variability, sanitary design and compatibility with processing environments. New technical developments in PAT tools, advances in chemometric modelling, robust data management tools and improved understanding of critical product and process parameters will facilitate further adoption of a PAT approach in cheese manufacture.